Professional Documents
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Intro to Neurons
1. Exitability and Secretions
a. electrical signals invade presynaptic terminals and elicit the exocytosis of NTs which can excite or inhibit
the adjacent neuron
2. Influence on nearby cells
a. some neurons in CNS and ganglions of PNS synapse locally to influence neighbors but not to distant sites
3. Influence on distant cells
a. some neurons can influence distant cells, transmitting information over very long distances
Ex: DRG
Ex: retina
Notable Structures
Neurites
Soma cell body
Axon branches that release NTs into the synaptic cleft and are received by the dendrites
Dendrite arborized branches that receive signals
Synapse space between axon and dendrite, where NTs must travel across to continue signal transduction
Myelin Sheath see glial cells
Collateral Axon Branch branch of the main axon that feeds back onto soma providing modulation of cell firing
Presynaptic Terminal where the NT will be released from
Nissl Body histological sign of rough ER, site of protein synthesis
Axon Hillock/Initial Segment connects soma to axon
Synaptic Bouton contains NTs waiting to undergo exocytosis; dense vesicles carry catecholamines, serotonin or
peptides where clear vesicles seen in motor neurons carry acetylcholine.
Cytoskeleton
The cytoskeleton is made of three filaments joined to each other, ER and vesicles by protein bridges. It functions in
the support and maintenance of neuronal shape as well as the transport of material between soma and neurites.
1. Microtubules
a. Is 100m long and 20nm in diameter and is made of polar tubulin molecules creating a pos and neg pole
b. Growth takes place by adding tubulin at the positive pole
c. MAPs (microtubule associated proteins -Tau Proteins) stabilize the microtubule & assist in transport
2. Neurofilaments
a. Most common filament with a diameter of 10nm (will essentially determine the diameter of the axon)
b. Undergo little turnover (unlike microtubules and microfilaments)
c. Create a scaffolding for the cytoskeleton of the neuron
3. Microfilaments
a. Are basically actin filaments at 5nm which form a network just below the cell membrane
b. Participate in growth cone during growth or repair after injury
(+) Nerve
Ending
1. Dynein
a. is an ATPase that moves in the
retrograde direction
b. it is also the motor protein responsible
for the movement of cilia and flagella
c. Nerve growth factor is one material
in particular that is endocytosed and
taken to the soma via retrograde
(-) Soma
(+) Nerve
Ending
3. Axoplasmic Flow
b. Is continuous but very slow, moving at about 1 mm/day
c. If it were not for MAPs, material exchange rates would be unsatisfactory and the cell would die
i. This is seen with drug use and aging
Glial Cells
4. Central Nervous System
a. ASTROCYTES
i. Sole storage for glycogen in the CNS and can convert/deliver as lactate as alternate ATP source in
the event of glucose supply interruption
ii. Regulates K+ microenvironment via Na/K pump and Na/K/Cl-cotxp
1. neuronal activity will [K+] and without this regulation, K+ can disrupt neuronal signaling
2. Spatial Buffering: the K+ from the ECF is distributed across the cytoplasm and its
neighbors via gap junctions
iii. Take up NTs from ECF which is crucial in terminating their actions
b. EPENDYMAL CELLS
i. GROUP 1 are the secretor cells of the choroid plexus and joined by tight junctions to stop water
and solutes passing paracellularly from the blood to CSF (BBB)
ii. GROUP 2 ependymocytes line the ventricles and central canal. They are joined by gap
junctions which allow flow around the cells for exchange between CSF and interstitial fluid. They
are also involved in circulation of the CSF within the CNS.
c. MICROGLIA
i. Are the macrophages of the CNS as well as playing a role in immune response
ii. The phagycytose debris from damaged cells and participate in scar formation
d. OLIGODENDROCYTES
i. Wrap 100 membrane layers around 1mm (with gaps of 1m) segments of several axons in its
vicinity to electrically insulate and increase conduction velocity of APs
5. Peripheral Nervous System
a. SCHWANN CELLS
i. Primary function is to myelinate ONE section of ONE axon
1. The axon will call out the schwann cell and instruct it to begin myelination (NOT IN CNS)
ii. Non-myelinating Schwann cells will envelope several small axons to create a Remak Fiber which
serves to regulate K+ ion concentration
iii. Central role in regeneration, forming a guide tube for the axonal segment to grow in as well as
secreting growth factors to induce axonal growth
Clinical Correlations
1. Gliosis
a. Hyperplasia and hypertrophy of astrocytes in response to CNS injury
b. Causes glial scars which limits axonal regeneration in the CNS
2. Regeneration of axons in the PNS
a. The distal end of a severed axon will degenerate (wallerian/anterograde degeneration) and the proximal
end sprouts new axons at 2mm/day
b. This is done with Schwann cells guide tube and release of growth factors
c. Deinervated cells will die within 3 weeks w/o neuronal activity
3. Regeneration of axons in the CNS
a. This is virtually impossible as there is no glial cell in the CNS that secretes enough Nerve growth factor to
elicit axonal growth
b. Additionally, oligodendrocytes do not form guide tubes and Schwann cells do and with the addition of
glial scars, regeneration is impossible.
4. Glial Tumors
a. 50% of brain tumors and 25% of spinal cord tumors are of glial origin, thus nearly all tumors are of glial
origin
b. Tumors of neuronal origin are extremely rare in both CNS and PNS
5. Viruses use Retrograde Transport
a. Some viruses use retrograde transport to reach the soma and infect the neuron
b. Examples include herpes and rabies, which enter the skin and work back to the soma.
Membrane potential (Vm) is known as the electrical difference between the interior and exterior of the cell wall
The separation of charge is always near the membrane where the Inside is Negative and the Outside is Positive
Enclosed in the cytosol or ECF there is macroscopic electroneutrality but at the membrane there IS a difference
Small changes in Ion flux (ie: 10-12 moles of Na+) will hardly affect the concentration gradient but it can
change the Vm by up to 100mV!
Resting Vm differences:
Resting Vm varies depending on the type of cell
Photoreceptors
-40mV
Skeletal Muscle
-90mV
Neurons
-65Mv
Ion Transport
1. Ion channels are responsible for allowing and
regulating ionic movement across the membrane
a. They are made of subunits surrounding a
central pore that is selective for a specific
ion.
Ionic Gradients
1. As stated, neurons have a Vm of about -65mV and the intra/extracellular ion concentrations are as follows
2. Potassium concentration can dramatically affect the resting potential in all excitable cells
a. Raising extracellular K+ decreases the amount of potassium loss, making the interior less negative
keeps it in
b. Reducing extracellular K increases the amount of potassium loss, making the interior more negative
+
forces it out
Ion Channels
1. The open/close state of the ion channels determines the membrane potential of the cell.
2. They are usually closed at rest but can be gated open by changes in potential, second messengers, NTs, etc
3. Membrane Conductance is based on the number of open channels and the conductance of that channel, thus:
gx
Membrane
conductance
Nx
number of
open channels
channel
conductance
gm = gNa + gK + gCl
a. In neurons, the net membrane conductance is based on the sum of each individual ion
b. K+ is the major influence and dwarfs the effects of the remaining ions
c. The Resting Potential is strongly influenced by the flux of K+ as well
Electrochemical Gradient
1. In the absence of control mechanisms, each ion will move in/out of the cell until it reaches its individual
equilibrium potential.
a. This is established when the electrochemical gradient reaches a point where its driving force
counterbalances the driving force of the ions concentration gradient and can be calculated as such
Nernst Equation
2. The electrochemical gradient of a given ion can be deduced from the equilibrium potential of the ion and the
membrane potential of the cell as seen in the following equation.
Electrochemical Gradient
= (Vm - EX)
Ix = gx (Vm Ex)
Im = INa + IK + ICl
4. As it can be seen with algebra, the previous two equations can be combined and since Im must be zero, so will the
new equation
Clinical Correlations
1. Death by Lethal Injection
a. Injection of KCl will increase extracellular potassium to the point where cells spontaneously depolarize and
in cardiac cells, will lead to death at high doses
2. Ischemic Cerebral Edema
a. Interruption of blood flow causes a failure of the Na/K-ATPase pump. This will result in the respective
ionic gradients dissipating where sodium will enter the cell causing water to follow and swell.
Graded Potentials
1. A stimulus to the sensory end of an afferent neuron (dendrite) will cause a local depolarization
a. it will also depolarize adjacent regions but weaker and weaker as it gets further from original site
2. while traveling along, charges will leak out of the membrane of the axon thus dying out as it travels which is
known as Decrement
a. The Length Constant () defines this exponential fall of a given structure/substance and can be
calculated
V = Vo exp (-x/)
= (arm/2ri)
a = radius
rm = cell surface resistance
ri = resistance along interior
b. Note that as radius (a) increases, so will the length constant meaning less decrement
Exposure
to
Light
Decrease
in
cGMP
Close
Na+
channels t
Decrease in [Na+]
hyperpolarizes
he Rod
Action Potentials
Propagated Response
Threshold for AP exists
Evoked by depolarization ONLY
Always overshoots zero mV
Mediated by voltage-gated channels
Amplitude independent of stimulus size All-or-None
No Summation
Amplitude is constant during propagation
Propagated over long distances
Clinical Correlations
1. Anosmia
a. Loss of olfactory sensation from head injury which severs/compressed the axons of the olfactory nerve
b. It may also develop as a function of aging; natural degeneration of a fraction of the olfactory nerves
2. Night Blindness
a. Vitamin A is where rhodopsin (the visual pigment in the rods) is derived from
b. Concequently, vitamin A deficient people will lack rhodopsin, hence night blindness as rods are
responsible for night vision
Refractoriness
1. Ball and Chain
a. Following a depolarization, the ball portion that carries a positive charge will lodge itself into the Na+
channel as it tried to exit the channel due to the positive charge intracellularly due to depolarization
rendering the channel INACTIVE.
b. Soon after, the ball will fall from the pore & the channel will close naturally, thus the channel is CLOSED
+
+
Clinical Correlations
MULTIPLE SCLEROSIS
Incidence is 1 in1000; causes demyelination of the CNS leading to
1. Effects CN-II (only cranial nerve myelinated by oligodendrocytes thus the only cranial nerve affected in MS)
a. Blurred vision, partial vision loss (bilat/unilat)
2. Effects Brain Stem
a. Hearing Loss axons dealing with CN-VII
b. Eye Movements weak Lateral Rectus (CN-VI) conjugate eye movements in brain stem
3. Motor Deficits
a. Weak/poor coordination lower limbs corticospinal tract
b. Speech deficits cerebellum
4. Sensory Deficits
a. Altered sensations from lesions in spinal cord
b. Sometimes, loss of pain, temperature, and in others, loss of proprioception
c. Parastesias in legs
5. Temperature Sensitivity
a. Rise in environmental temperature is associated with faster conduction velocity but duration and amplitude
decrease; thus, playing into the built in safety factor MS patients are worse in warm weather and
sometimes better in cooler weather.
13 Synaptic Transmission
Electrical vs. Chemical Synapses
1. Electrical Synapse
a. In the CNS, occur in the spinal cord, hippocampus, mesensephalic nucleus and retina b/w horizontal cells
b. Gap Junctions are found at electrical synapses, spanning both cell membranes of adjacent cells
i. Gap junctions also occur b/w astrocytes allowing these glial cells to function in syncytium when
buffering K+ ions
c. Electrical synapses also play a role in cardiac signaling and some epithelial cells of various organs
d. NOTE: the number electrical synapses in the CNS are Dwarfed by chemical synapses, thus forgetem
2. Chemical Synapses
a. Most synapses are chemical, where a NT from the presynaptic bouton is released across the synapse and
play on a receptor in the postsynaptic cell
b. Active Zone: where exocytosis
occurs in presynaptic membrane
c. Dense Regions: where NT is received
in the postsynaptic membrane
3. Location of Synapse and Function
a. AxoDendritic excitatory on firing rate
b. AxoSomatic inhibitory on firing rate
c. AxoAxonic inhibitory on NT release
3. Spatial Summation
a. Very simply, the sum of the excitatory currents will add to yield a larger EPSP than either of then alone
4. Temporal Summation
a. Multiple impulses arriving so close together that they add to one another because the effect of the previous
impulse has not relaxed back to the resting state, thus adding on top of each other
5. Important Points
a. note that both temporal summation and spatial summation can occur together
b. These types of summation can occur with IPSPs as well
Clinical Correlations
1. Tetanus Toxin
a. Caused by infection of Colostridium tetani via skin wound
b. Prevents normal release of inhibitory NTs
i. Disables the inhibition portion of the reflex arc thus resulting in hyperreflexia
ii. Absence of reciprocal control of agonist/antagonist muscles produces muscle spasms
2. Strychnine Poisioning
a. A plant alkaloid that blocks Glycine receptors in the CNS with similar sx/sx to Tetanus
3. Cocaine
a. Affects reuptake of transmitters by nerve endings, particularly catecholamines
b. Prolongs their presence in the synaptic cleft, particularly serotonin (dopamine) thus its addictiveness
4. Morphine
a. Administered into the subarachnoid space for analgesic effects
b. Acts as an agonist for the receptors mediating the presynaptic inhibition of C-fibers that relay pain
14 Neuromuscular Transmission
Muscle Fibers Activated by Motor Neuron
1. Motor Unit
a. Comprised of a motor neuron (soma, myelinated axon, NMJ) and the skeletal muscle fiber it innervates
b. The number of muscles under control of a single neuron depends on location and the need for fine control
i. The extraocular muscles and some in the hand, have some 10 fibers per neuron (fine motor control)
ii. The postural muscles can have up to 2000 fibers controlled by one neuron (no need for fine motor)
2. Motor Nuclei
a. Have cell bodies distributed over more
than one spinal segment that fall within
a motor nucleus
b. The axons from this nucleus leave the
cord via ventral roots via spinal nerves
then join together in the peripheral
nerve to reach the target muscle
3. At the target fiber:
a. There is profuse branching, the axon loses its myelination and rests its presynaptic boutons on the fiber
b. The central region of the muscle that will revieve the NT is called the Motor End Plate
c. This presynaptic terminal and boutons are covered by Schwann cells without myelin (Remak Fiber)
4. Notable Features of NM Transmission
a. Each muscle fiber has only ONE NMJ
b. The NMJ is where ACh is released by Ca2+ dependant exocytosis and binds to its Ionotropic receptor
c. The transmission at each NMJ is so effective that each impulse in the neuron will release ACh to excite
the muscle
d. No inhibitory synapses on the muscle fiber, inhibition must be applied to the neuron, not the muscle.
2. Life Cycle
a. Unusual for a NT in
that it is Rapidly
degraded in the cleft
by AChE and the
product is reabsorbed to
be reformed into ACh
Microenvironment of NMJ
1. Acetylcholine Release Site
a. Remember the active zone from lecture 13; release site of NTthey are positioned directly opposite the
large number of ACh receptors in the postsynaptic cell (also see pic above)
b. Diffusion distance is very short and the diffusion time is virtually nil and the AChE is waiting to do its job
2. Voltage-Gated Channel Position in and around NMJ
a.
b.
c.
d.
e.
Blocks Na-channels to
irreversibly prevent the
arrival of the original impulse
No APs = cardiac/resp arrest
-condotoxin
Snail Toxin; irreversibly binds
to calcium channels thus
stopping the capacity for
exocytosis of ACh
Botulinum Toxin
-Latrotoxin
Neostigmine &
Physostigmine
Tubocurarine
-bungaratoxin
AChRelease
Botulinium
-condotoxin
-Latrotoxin
Physostegmine
Neostegmine
Sarin
Tabulin
Carbachol (carbamylcholine)
Nicotine
succinylcholine
Turbocurarine (curare)
Pancuronium
-bungarotoxin
Clinical Correlations
1. Muscle Relaxants
a. as seen above, are useful in surgery
2. Electromyographic Recordings (EMG)
a. Monitors muscle impulse activity via extracellular electrical recording electrodes inserted into the muscle
b. Used to diagnose various muscular disorders including Myasthenia Gravis based on irregular impulse
responses
3. Myopathies
a. Some types of muscle weaknesses do NOT originate in the NMJ, they originate in the muscle fiber itself
b. Other muscular dystrophies have malfunctioning cytoskeletons lacking certain vital proteins
c. Some myotonias have abnormally slow relaxation times for the muscle fibers due to ion channel deficits
15 Neurotransmitter Release
Storage in Vesicles
1. Each molecule stores a Small-Molecule Transmitter and a Neuropeptide
a. SMT synthesized in the cytosol and taken up into empty vesicles for pre-release storage at active zone
b. Neuropeptides synthesized in the soma, stored in vesicles and sent to nerve ending via anterograde txp
2. Two Populations of Vesicles
a. Clear Vesicles contain small molecular transmitters (ACh, Glutamate, etc)
i. Low nerve stimulation (10Hz) causes a rise in [Ca+] near the active zone causing preferential
exocytosis of the small clear vesicles
b. Dense Cored Vesicles most contain Peptides but some contain smts like NE and Serotonin
i. High nerve stimulation rates (100Hz) cause the rise in [Ca+] to spread further thus causing
exocytosis of the large dense cored vesicles
+
3. Absorption of NT into Vesicles
NT+/H+ NT
a. Dependant on an H+ gradient; the H+-ATPase pumps H+ into the
antiport
vesicle so that this created gradient can be used by an Antiport
H+
membrane protein releasing hydrogen in exchange for the given NT
H+-ATPase
(ie: dopamine)
H+ exch.
1. Proteins needed for Exocytosis in Vesicular Membrane
a. Synapsin: initially holds vesicle in place in the cytoskeleton then liberates said vesicles from cytoskeleton
b. Rab Proteins: trafficking/targeting vesicles to site of eventual exocytosis
c. Synaptobrevin & Synaptotagmin: docking-priming vesicle with nerve membrane
d. Synaptophysin: forms fusion pore in nerve terminal membrane
Calcium-Dependant Exocytosis
1. Ca+ channels are adjacent to active zones and open to allow Ca+ into the presynaptic ending in the event of an
action potential in an effort to liberate the vesicles containing the NT
2. The RISING PHASE of Ca+ is quick but the FALLING PHASE is slow which reflects the slow removal
mechanisms used to bring the concentration of Ca+ to its normal value
a. There is a calcium-ATPase and Ca+/Na+-exchanger used to extrude Ca+ ions
b. There is also a sequestering system within the smooth ER to save and use Ca+ ions later
SNARE Hypothesis
1.
2.
3.
4.
5.
Transmitter Release
1. Exocytosis is governed by the probability of release (p) times the number of vesicles (n) thus, pn
2. Reducing Ca+ entry influences p
a. This can be seen if Mg2+ replaces Ca2+ which blocks the Ca2+-channel and reduces the EPP accordingly
b. This change in the EPP is also evident when noting the quantal fluctuations with reduced Ca2+
3. Spontaneous release of ACh from Nerve Ending
a. In the absence of stimulation, there exists small transient depolarizations (1mV) called miniEPPs
b. miniEPPs indicate spontaneous release of ACh, seen in all other synapses as well
QUANTA
4. Neurotransmitters are released in packets called quanta which contain a certain # of molecules of transmitter
a. In motor nerve endings ~7000 molecules
b. For glutamate ~4000 molecules
5. The number of quanta released for a single impulse is called the quantum size
a. this can be estimated for a NMJ bathed in low [Ca2+] by
Mean Quantum Content = (mean size of EPP) / (mean size of miniEPP)
b. IN TRIAL: low EPPs (close to a 1mV miniEPP) the mean quantum size was 1 (ie: one single vesicle)
IN REALITY: at the NMJ the mean quantum content is ~200 (ie: 200 vesicles each containing ~7000 molecules)
c. Note that at all other synapses the mean quantal size is usually only 1 vesicle (based on this equation)
Clinical Correlations
1. HYPOcalcemia (think of a differential diagnosis of diGeorge Syndrome)
a. Often a cause of hypoparathyroidism (physiology- PTH regulates calcium levels-bone/kidney/gut)
b. Extracellular calcium is needed to neutralize the negative charges in the extracellular matrix so in its
absence, the outside becomes more negative which makes the membrane difference from outside to inside
will get close to threshold, which will cause eventual unwanted depolarizations.
c. These depolarizations cause repetitive firing of APs resulting in tetany and parasthesia
d. Calcium also helps stabilize the membrane and without it, the cells becomes leaky which again causes
unwanted depolarizations resulting in the same sx/sx though this cause is reversible
2. Botulinum Toxin
a. Microinjections used to treat dystonias (irregular/troublesome clonic/rhythmic contractions)
b. Also used cosmetically to reduce facial wrinkles
3. Snake Venom
a. Some venom (not the same as alpha-bungarotoxin from cobra) blocks ACh release by irreversibly binding
to actin resulting in paralysis which can be fatal if it effects respiration.
16 Neurotransmitter Systems
Classes of Transmitters
1. Four General Classes
a. Amino Acids mediate fast responses (within ms) in the CNS
b. Amines some (ie: ACh and serotonin) also mediate fast responses in the PNS, NMJ & postganglionic
neurons of the ANS
c. Peptides include CCK, substance P, VIP, etc, all of which are Metabotropic thus have slow responses
d. Gases includes NO and CO
Receptor Type
Nicotinic (nAChR)
Muscarinic (mAChR)
Alpha adrenoceptor
Beta adrenoceptor
AMPA
NMDA
GABAA
GABAB
Glycine
Agonist
Nicotine
Muscarine
Phenylephrine
Isoproterenol
AMPA
NMDA
Muscimol
Baclofen
Glycine
Antagonist
D-tubocurarine
Atropine
Phenoxybenzamine
Propranolol
CNQX
AP5
Bicuculline
Phaclofen
Strychnine
Transmitter Removal/Degredation
1. Excluding ACh, NO and Peptides, all transmitters are removed rapidly via transporters in the nerve ending or
by glial cells
2. Noradrenaline and Serotonin are absorbed then broken down by MAOs from the outer mitochondrial membrane
in the nerve ending
Muscarinic Receptors
ACh released by postganglionic parasympathetic nerves (ANS) affect a muscarinic receptor to elicit a response which can be
defined by the subgroup that the mAChR falls into
Catecholamines
1. Synthesis
TYROSINE
L-DOPA
DOPAMINE
Dopa Decarboxylase
*Rate limiting Step
NOREPI
Dopamine -Hydroxylase
EPINEPHRINE
PMNT
Amino Acids
1. Glycine
a. Main inhibitory NT in the spinal cord working via Ionotropic receptor selective to Cl- ions
b. The glycine-receptor has similar structure to nAChR but needs THREE molec of glycine to open channel
2. GABA
a. Main inhibitory NT in the brainstem
b. GABAA mediating fast IPSPs working via Ionotropic receptors similar to Glycine and nAChR
i. Needs TWO molecules to bind to the -subunit to open the channel
ii. The GABAA receptor also binds a wide range of inhibitory medications (ex: anit-epileptic meds)
c. GABAB work slowly via Metabotropic receptors to open potassium channels to inhibit the
postsynaptic neuron
3. Glutamate
a. AMPA Receptor
i. Typical Na+-channel
b. NMDA Receptor
i. Blocked by residing Mg2+ ion which leaves under influence
of a very large depolarization usually due to the summation
of many EPSPs
ii. When it is unblocked, it allows Ca2+ entry into the postsynaptic
cell where this calcium plays a role in alterations of enzyme
activity
3. Dopamine
a. Receptors
i. D 1 - like (D 1 and D 5) increase cAMP production
ii. D 2 - like (D 2 , D 3 and D 4) inhibit cAMP production
b. Dopaminergic cells in the substantia nigra project to the basal ganglias striatum (caudate n. & Putnam)
i. Strial Neurons in the substantia nigra have both D1 and D2 receptors
c. Dopaminergic cells in the ventral tegmental area project to the hippocampus (memory formation),
nucleus accumbens and frontal lobe cortex (planning/attitude)
4. Enkephalin
a. An Opoid peptide released from local interneurons, exerts presynaptic inhibition at the synapses of
nociceptors (pain) on projected neurons
Clinical Correlations
1. Pilocarpine
a. ACh-mimmetic drug acting as a mAChR agonist in the parasympathetic nervous system
b. Acts on ciliary muscles and drains fluid via Canal of Schlemm which pressure and used to treat glaucoma
2. Beta-Blockers
a. Antagonist of 1-receptors; used to treat HTN by vasoconstriction, HR and contractility
3. Asthmatic Bronchodialator
a. Antagonist of 2-receptor, used to relax and dilate bronchiolar smooth muscles
4. Nasal Congestion Relief
a. Antagonist of 1-receptors used as a nasal vasoconstrictor hence a reduction in congestion
5. Horners Syndrome
a. Unilateral loss of sympathetic input causes this unopposed parasympathetic influence to manifest with a
constricted pupil (miosis), drooped eyelid, inactivated sweat glands (dry face) and a retracted eyeball
b. This unilateral lesion is in the CNS as such:
hypothalamus spinal cord superior cervical ganglion ciliary nerve
Blood
Plasma
70ml (15%)
Interstitial Fluid
260ml (55%)
CSF
150ml (30%)
1. Circulation of CSF
a. Remember lateral ventricles are connected to third ventricle via Monroe
b. Third ventricle connected to fourth via Cerebral Aqueduct (Sylvius)
c. Fourth ventricle flows CSF into subarachnoid space of spinal cord via Magendie
2. Spinal Tap/Lumbar Puncture
a. Done at L3-L4
b. Used to attain and analyze CSF composition and abnormalities
c. Also used to test ICP (but can be inaccurate in the event of an obstruction)
3. Composition of CSF
a. 6 major differences between CSF and Plasma
NOTE:
1.
Protein
Component CSF Plasma
a. CSF is untrafiltrate thus,
pH
7.33
7.41
very little protein content
Protein
35
7000
2. pH
Glucose
60
90
CSF is LOWER
a. reflects said low protein
K+
2.8
4.5
count as well as a poor
Ca2+
1.1
2.4
buffering system
CSF is HIGHER
Cl120
100
4. Function of CSF
a. Maintains constant extracellular environment
b. Provides a means for removing the brains metabolites
c. Mediates ventilation rates via exhibiting pH
d. Mechanical cushion (trauma/movement)
Cerebrospinal Fluid
1. Choroid Plexus
a. Site of CSF production and is found in most of the lining of the ventricles (not found in cerebral aqueduct)
b. Constantly secreting isotonic CSF into the ventricles
c. Joined by tight junctions excluding paracellular transport thus creating the blood-CSF-barrier
d. Production is constant at 500ml/day and in normal conditions is absorbed at the same rate
i. HYDROCEPHALUS can be caused when absorption is too slow or production is too fast
2. Transport of Ions
a. There is much movement of ions via multiple channels and transporting proteins on both sides of the
secretory cell but the NET MOVEMENT of ions is Na+, K+ and Cl- into the ventricles followed by water
via osmosis
b. The ions being followed by osmosis ensures that the movement of fluid is ISOTONIC
3. Absorption
a. Takes place in the SSS by the Arachnoid Villi
b. It is a pressure driven absorption where the CSF is at higher pressure than the venous system
c. It is absorbed into vacuoles which cross thru the cell and are emptied into the venous sinus
CSF Abnormalities
1. Composition Changes Used as Diagnostic Tool
Condition
Cells (mm3)
Protein
(mg/dl)
Glucose
(mg/dl)
Normal
Bacterial Meningitis
Viral Meningitis
Brain Tumor/Abscess
MS
Guillian-Barre
Subarachnoid Hemorrhage
<5
HIGH 1000
High 500
High 500
Normal
~10
RBCs
35
HIGH 500
High 500
High 500
Normal
>50
High
60
Low 20
Normal
Normal/Low
Normal
Normal
Normal
Edema
Disturbances of the blood supply that interfere with the normal well regulated exchange of solutes and water between
blood and brain can cause edema and there are two types
1. Vasogenic Edema
a. Damage to brain capillaries rendering them more permeable than normal (ie: leaky)
b. Usually occurs in the White Matter
2. Cytotoxic Edema
a. Inadequate blood supply to neurons and glia thus failing to deliver proper O2 and Glucose
b. This starves the Na/K pump results in a dissipation of ionic gradients and the cell swells with ensuing
damage
c. Usually occurs in the Gray Matter
Clinical Correlations
1. Blood Supply for Tumors
a. Lack any tight junctions and the paracellular flow of nutrients only promotes the growth of the tumor
2. Congenital Hydrocephalus
a. Blockage of the cerebral aqueduct (or absence of the formation)
b. Dandy-Walker Syndrome: F.O. Lushka and Magendie fail to form
3. Adverse Effects of Increased ICP
a. Sx/sx of an increase above 15mmHg include
i. Nausea
ii. Bradycardia
iii. HTN
iv. LOC
v. Blurred Vision (due to papilledema increasing pressure in subarachnoid space near CN-2)
22 Sensory Systems
Introduction
The Sensory System is designed to detect physical stimulus and translate it into cell activity
o Translation of the stimuli is known as transduction
The Receptors transmit onto second-order neurons which are part of the particular sensory pathway
The information reaches cortex to be interpreted/perceived
o most sensory areas are within the parietal, occipital, temporal or insular lobes
Thus, the basic pattern is Stimulus Receptor Pathway Perceived Behavior
Sensory System
Somatosensory
Mechanoreceptors
Thermoreceptors
Chemoreceptors
Photoreceptors
Mechanoreceptors
Mechanoreceptors
Chemoreceptors
Chemoreceptors
Visual
Vestibular
Auditory
Olfactory
Gustatory
Stimulus Attributes
1. Intensity
a. Refers to the amplitude (ie: quantity) of the stimulus
b. Sub-threshold stimuli can elicit a small receptor potential but may not induce an Action Potential
c. FREQUENCY CODE
i. Assuming receptor potentials are above threshold, the higher the stimulus intensity is the more
action potentials will be generated per unit time
d. POPULATION CODE:
i. High intensity stimuli can activate more individual axons than a low intensity stimulus
ii. Ex: press harder and harder on your hand, stimulates a larger area, thus more axon stimulation
2. Duration
a. Defined by the difference between the start and end time of the stimulus
b. Receptor adaption: the disappearance of a sensation induced by a stimulus when the duration is too long
i. example: the disappearance of the feeling of wearing clothes all day even though you felt them
when you put them on
c. SLOW ADAPTING RECEPTORS
i. Used for constant monitoring; important for regulatory function of tight physiologic windows
ii. They remain depolarized for the duration of the stimulus and maintain a constant output of APs
d. RAPID ADAPTING RECEPTORS
i. Only signal at the onset of stimulus where the receptor potential quickly returns to baseline
ii. No further APs are generated despite the persistence of the stimulus
iii. Much better equipped for sensitivity to changes and not constant stimulation
4. Location
a. Understanding the location of a stimulus is defined by the
receptive field of the stimulated neuron
i. Receptive Field: the area monitored by a single neuron; ie:
the area where a stimulus would induce a response
b. If the stimulus is placed within the receptive field, assuming it is
above threshold, it will elicit an AP
c. If the stimulus is placed outside of the receptive field, there will
never be an AP on that particular neuron
3. Lateral Inhibition
a. A situation where a first-order neuron stimulates an interneuron which will relay that stimulus to an
adjacent second-order neuron only it is inhibiting that adjacent neuron
23 Somatosensory System
Introduction
Cutaneous Receptors
1. Touch
Ruffini and Pacinian
Deeper in tissue with large receptive fields
a. Merkels Disks discriminating touch
b. Ruffinis Endings skin stretch
2. Vibration
a. Meissners Corpuscles highest sensitivity for low frequencies 50Hz
b. Pacinian Corpuscles sensitivity for higher frequencies near 300Hz
3. Pain and Temperature
a. Transduced by free nerve endings (be it mechanosensitive or thermosensitive receptors)
Proprioception
1. Muscle Spindles
a. Found in the extrafusal fibers of working musculature
b. The receptor is of rapidly adapiting nature using
1-a afferents form afferent limb of the myotactic reflex
Segmental Organization
1. Spinal Nerves
a. Remember Gross Anatomy:
i. spinal nerve-C1 emerges above vertebra-C1 and spinal nerve-C8 emerges below vertebra-C7
ii. spinal nerve-T1 emerges below vertebra-T1 and this pattern continues for the remainder
2. Dermatomes
C2: back of the head
C6: posterior forearm to thumb
C7: posterior forearm to pinkey
C8: middle finger
T4: nipple line
T10: umbilicus
L1: groin
L5: big toe
S1: little toe
2. Anterolateral System
a. Used to relay Pain and Temperature
b. Also enter dorsal root and synapse in dorsal horn onto second-order neurons that cross the anterior white
commissure and ascent in the ventral white matter (yellow)
3. Lissauers Tract
a. Very clinically relevant relative to the ALS
b. This tract gives an alternate route for pain and temperature to ascend in the event that there is an injury to
a section of the spinal cord as seen with a hemisection in Brown Sequard Syndrome
c. Pain and temperature can ascend one or two sections past the injury in the Dorsolateral Fasciculus
(aka Zone of Lissauer, then cross over and rejoin the ALS
Brown Sequard
Syndrome
24 Touch
General Info for Touch Pathway
Consists of a 3-Neuron-Chain
o First-order neurons: somatosensory afferents (peripheral nerves)
o Second-order neurons: fibers crossing the midline and terminating in the thalamus
o Third-order neurons: running in posterior limb of internal capsule and ending in S1 (primary sensory)
1. Body
Organization of S-1
1. Topographical Organization
a. A quick look at a topographical map of S1 can
quickly define where in S1 different parts of the
body are referred; such a map is known as a
Somatotopic Map
2. Organization in Columns
a. Input processing neurons are organized in the cortex
based on the speed of the receptor that is sending it the
information.
b. Thus, Slowly Adapting Receptors (SA) are organized in one column and Rapidly Adapting Receptors are
organized in the adjacent column; so you have a sequence of columns as SA-RA-SA-RAand so on.
3. Input Layer 4
a. As it is already know, the cortex has 6 layers (1 at the pia matter deeper to 6 at the white matter)
b. Layer-4 of S1 received input from the thalamus (VPL/VPM) where the 3rd-order neurons are from
Two-Point Discrimination
1. Variation Throughout the Body
a. The threshold and resolution varies across the body
b. Much higher resolutions (inverse of threshold) are found in the hands and feet and lower resolutions are
found in places like the forearm, lower leg and back
2. Dependant Factors
a. Receptor density
i. More receptors will increase resolution
b. Receptive field size
i. The smaller the field, the higher the resolution will be
c. Size of cortical area involved
i. The larger the cortical area involved in S1 the greater the resolution will be
d. Special mechanisms, if any
i. Mechanisms such as lateral inhibition can increase resolution (receptive fields, lec.22, p2)
Clinical Correlations
NEUROLOGIC EXAMINATIONS
1. Touch/Pain, Vibration and Proprioception
a. Touch and Pain: using a sharp and dull object, poke around and ask sharp or dull?
b. Vibration: often the first sense lost in peripheral neuropathies; test by touching tuning fork to bony
prominence and do it both with and without activating the fork to make sure the person is truthful
c. Proprioception: grasp the finger from the sides and pull up or down and ask up or down?
2. Complex Tactile Function
a. Two-Point Discrimination: use a bent paper clip at different widths and ask one or two?
b. Stereognosis: give the person a familiar object and ask what is this?
c. Graphesthesia: the patient should be able to identify letters drawn in the palm with a blunt object
i. Inability to do so might indicate a cortical lesion
NEUROPATHIES
1. Tabes Dorsalis
a. Destruction of DRG and large myelinated fibers due to infection with syphilis
b. TVP becomes very deficient but TP remain almost unaffected (think of what fibers control each modality)
2. Phantom Limb Sensations
a. A phenomenon where a person thinks they are feeling pain in a recently amputated limb and this pain is
exacerbated/elicited when other parts of the body are stimulated (think of hand and face example)
b. This can be explained by rearrangement of the cortical input from an existing part of the body to the
cortical area that once controlled this now missing limb
i. For example: the neurons from the face region of the cortex migrate to where the hand used to be
25 Pain
Major Classifications
1. Nociceptive pain
a. Direct stimuli of nociceptors and have the potential to cause tissue damage
2. Neuropathic pain
a. CANNOT be explained by simple activation of nociceptors by tissue damage
b. Includes pain where the mechanism is a site of atypical somatosensory processing the PNS or CNS
Pain Pathway
2. Trigeminal Pathway
Nociceptors
1. Activation of Nociceptors
a. Nociceptors can be activated by mechanical or thermal stimuli
b. In the event of tissue damage, many chemicals are released which can activate chemical nociceptors
i. Bradykinin from the blood
ii. Histamine from mast cells
iii. Potassium from damaged cells (think of what extracellular K+ can do to membrane potential!)
2. Hyperalgesia
a. Enhanced sensitivity and responsivity to an area around damaged tissue
b. This is caused by increasing nociceptor sensitivity caused by chemicals released at the site of trauma
i. Prostaglandins and Leukotrienes from damaged cells
ii. Substance P from primary afferent pain fibers
Pain Control
1. Gate Control in the Spinal Cord
a. Very simply put, if a touch fiber is stimulated, it will meet
the pain fiber in the dorsal horn (similar to referred pain)
and activate an interneuron that will inhibit the synapse
between the first and second order pain fibers
b. The touch fiber causes the interneuron to release Enkephalin
(an endogenous opoid) which inhibits the pain fiber
c. Opoids can AP duration, EPSP duration and they can
also hyperpolarize the second-order neuron
2. Descending Regulation
a. Serotonergic and Noradrenergic fibers from the brainstem
will act identically as seen in the gate control pathway
b. They synapse on this opoidergic interneuron where they
control the transmission of the pain fibers
Clinical Correlations
1. Neurologic Examination of Pain and Temperature
a. Pain: can be tested along with touch using an object having a dull and sharp side (see lec. 24)
b. Temperature: tested using test tubes, one with hot water and the other with cold water, touch in random
places and ask the question is that hot or cold?
2. Headache
a. There are NO nociceptors in the brain so in order to feel pain, a neighboring structure must be stimulated
i. Blood vessel wall
ii. Dura matter
iii. Skull Periost, etc
3. Aspirin
a. As with other NSAIDs, it will cyclooxygenase resulting in a decrease of PGEs
b. PGEs are responsible for sensitizing sensory afferents, so in their absence, pain will be dulled
4. Surgical Management
a. In extreme cases, such as terminal cancer patients, the DRG is removed to stop pain transmission
b. This is known as a Dorsal Rhizotomy
5. Acupuncture
a. Causes a release of opioid peptides and will decrease pain fiber transmission (see above pain control)
26 Visual System
Anatomy of the Eye
Optic Disk/Blindspot
Visual Acuity
Defined as the ability to distinguish between two points and can be measured by the visual angle between them
1. Dependant Factors
a. Density of Photoreceptors best at the fovea, better at the macula and absent at the optic disk
b. Lens Accommodation inability to focus image on the retinal results in a blurry image which acuity
Clinical Correlations
1. Emmetropia
a. Also knows as normal-sightedness
b. This is when the length of the eyeball matches correctly with the refractive power of the optical apparatus
2. Myopia
a. Also known as Nearsightedness
b. The lens is too powerful for the length of the eyeball so the image is focused before reaching the retina
c. Remember that near vision calls for high refractive power therefore with myopia near vision is still good
d. The use of Concave (-)D glasses will correctly place the image more posterior to match the retina
3. Hyperopia
a. Also known as Farsightedness
b. The lens is too weak for the length of the eye so the imaged is focused beyond the retina
c. Remember that far vision calls for lower refractive power therefore with hyperopia far vision is still good
d. The use of Convex (+)D glasses will correctly place image more anterior to match the retina
27 The Retina
Photoreceptors Rods & Cones
STRUCTURE
1. Outer Segment:
a. oriented toward the RPE
b. contains visual pigment for photoreceptor transduction
2. Inner Segment:
a. directed toward the center of the eyeball
b. forms synapses which transmit the visual info on the retinal cells (bipolar/horizontal cells)
3. Disk Shedding
a. The outer segment renews disks from the bottom up, the top disks are shed and phagocytosed by RPE cells
PROPERTIES
1. Rods
a. Cellular amplification mechanism is well developed which light sensitivity enables vision in the dark
b. Temporal summation is poor (distinguish between two flashes of light)
2. Cones
a. As there is no need, amplification is low, thus less sensitive to light, working better in bright conditions
b. Temporal summation is much better than rods
c. Three different types of cones allow color vision
d. Convergence is low, thus increasing spatial resolution (visual acuity) showing better vision in the light
3. Distriubtion
a. Rods/Cones are NOT evenly distributed, there are NO rods in the fovea, thus no central vision in the dark
Phototransduction
1. The Dark Current
a. Photoreceptors are depolarized in the dark; (ie: in the absence of light stimulation)
b. In the dark, visual pigment is inactive, thus the G-protein does NOT activate cGMP phosphodiesterase
c. If the cGMP phosphodiesterase is left inactive, the intracellular cGMP can gate the cGMP-gated Na+
channel to its open state (thus depolarization)
d. In its state of depolarization, the photoreceptor will release its NT, Glutamate (just as any other
depolarized would do)
2. Phototransduction Process
Light
i. Light activates visual pigment
ii. Visual pigment activates G-protein
iii. G-protein activates cGMP phosphodiesterase
iv. cGMP phosphodiesterase metabolizes intracellular cGMP
v. A intracellular cGMP will close the Na+ channel
vi. Closing Na+ hyperpolarizes, thus stopping glutamate
a. ON vs, OFF
i. ON Bipolar cells named so because they are depolarized when the light is turned ON
ii. OFF Bipolar cells named so because they are depolarized in the dark, thus when the light is OFF
iii. The depolarization or hyperpolarization of the bipolar cell depends on the synapse between the
photoreceptor and the bipolar cell
b. OFF Bipolar Cell
i. Have Ionotropic glutamate receptors which when stimulated by the release of glutamate, will
depolarize the bipolar cell
ii. As we have seen, photoreceptors release glutamate in the dark, so OFF bipolar cells are therefore
depolarized in the dark
c. ON Bipolar Cells
i. Have Metabotropic glutamate receptors which have an inhibitory effect when stimulated by the
release of glutamate from photoreceptors
ii. When light hits the photoreceptor, it hyperpolarizes and stops glutamate release, therefore stopping
the release of the inhibitor transmitter glutamate
iii. In the absence of the inhibitor glutamate with, the ON bipolar cell will depolarize (dis-inhibited)
3. Horizontal Cells
a. Normally, ON bipolar cells are depolarized when light is being shined onto the center of its receptive field
b. Horizontal cells are responsible for the lateral inhibitory effect needed to depolarize an ON bipolar cell in
the event that the light has not been placed directly in its receptive field but in the surrounding area
c. The sequence of events is as follows:
The peripheral photoreceptor is hyperpolarized
due to light exposure thus stopping the release of
glutamate
LIGHT
I.
4. Ganglion Cells
a. ganglion cells are responsible for generating action potentials (see above)
b. The ganglion cells are named ON and OFF for the same reasons as the bipolar cells
c. ON Ganglion Cells
i. if the light is shining directly into the center of an ON center ganglion cell, the frequency and
number of APs generated will increase as they are meant to work better in the light
ii. if light is shining on the surrounding field, the APs from the ON ganglion cell will decrease
d. OFF Ganglion Cells
i. Work exactly opposite; light to the center will decrease the number and frequency of APs
ii. Light to the periphery will increase the number of APs generated as they are meant to work
better in the dark
Clinical Correlations
1. Retinitis Pigmentosa
a. Genetic disease in which rods preferentially degenerate
b. Night blindness is the earliest sx, followed by peripheral vision and tunnel vision, eventually causing
total blindness
c. The accumulation of pigment (seen thru opthalmoscope) gave the name of the disease
d. The photoreceptor degeneration is not cleaned up by the phagocytes of the RPE (see above disk shedding)
2. Night Blindness (Nyctalopia)
a. Effects vitamin-A deficient people as the Retinal is derived from it
b. A very necessary part of the Opsin/Retinal combination that forms the photoreceptor pigment
3. Color Blindness
a. Lack of a particular type of cone, most common is the x-linked red-green colorblindness prevalent in
b. There are two types/conditions that cause red-green colorblindess
i. Protanopia: loss of the red-cone (L-cones)
ii. Deuteranopia: loss of the green-cone (M-cones)
28 Visual Pathways
The Visual Field
Is the total space seen when the eye is fixed looking straight ahead toward the center of the visual field
1. Divisions
a. LEFT VS RIGHT
i. Divided into the left and right hemifield but more accurately called the nasal and temporal field
ii. Usually spans from 60o to 90o (so for the right eye that would be going from nasal to temporal)
b. UP VS DOWN
i. Top and bottom visual fields are split into superior and inferior fields
2. Pathway of Light
a. The Superior half of the Visual field is reflected
onto the Inferior half of the Retinal field
b. The Nasal half of the Visual field is reflected onto
the Temporal half of the Retinal field (and vice-versa)
c. SUMMARY: the visual field reflects upside down
and opposite on the retinal field
Neuronal Pathways
1. Projection of the Retinal Ganglion Cells
a. As seen before, the retinal ganglion cells are the output neurons of the retina
b. They send their info to eventually reach the primary visual cortex V1 via the following pathway
Retinal
Ganglion
Cells
Optic
Disk
Optic
Nerve
Optic
Chiasm
LGN
(thalamus)
Primary
Visual
Cortex V1
Organization of V1
1. Broadmann Area 17
a. The primary visual cortex V1 is located in
area-17, most of which is on the medial aspect
b. There is a superior and inferior bank divided by the
Calcarine sulcus (reminder: opposite relations to visual fields)
c. Blood supply primarily from the calcarine branches of
The posterior cerebral artery.
2. Retinoptic Organization of V1
a. This is much easier represented with a picture but in summary:
i. The left visual field reflects to the right V1 and vice-versa
ii. The superior visual field reflects to the inferior V1 and vice-versa
iii. Macular/central vision reflects to the superficial V1 and peripheral vision to the deeper V1
3. Columnar Organization of V1
a. OCCULAR DOMINANCE COLUMNS
i. As seen above, visual fields from both the left and right eye can relay to a single side of V1
however that information does not actually reach identical locations
ii. There are separate/individual areas (columns) dedicated to the input from each eye
iii. Thus there are (C) Contralateral Columns and (I) Ipsilateral Columns in both the left and right
V1
b. ORIENTATION COLUMNS
i. In this case, there are columns of V1 that have a preference to the orientation of the image in the
visual field
ii. There are various orientation columns which have varying preferences such as vertical and
horizontal light as well as the intermediate variations
Parallel Pathways
1. DEPTH & MOTION (Where?)
a. Starts in the Magnocellular neurons (M-ganglion cells) of the retina, synapse in 2-of-6 layers in the LGN
b. They leave the LGN and follow the Dorsal (parietal) pathway (similar to the inferior visual field)
2. FORM & COLOR (What?)
a. Starts in the Parvocellular neurons (P-ganglion cells) of the retina, synapse in 4-of-6 layers in the LGN
b. They leave the LGN and follow the Ventral (temporal) pathway (similar to the superior visual field)
Clinical Correlations
1. Neurologic Exam of Visual Fields
a. Using the confrontational visual field test each quadrant of the field can be tested individually
b. Patient is double-arms length away and stare at each other with opposite eyes then place hand gradually
into each field individually
c. Assuming the examiner has normal vision, the patient and examiner should see the hand at the same time!
2. Visual Pathway Lesions
Understand this summary table and be able to draw it onto a picture
29 Eye Movements
Types of Eye Movements
CONJUGATE EYE MOVEMENTS (eyes are moving together in stereo)
1. Saccadic Movement/Gaze
a. Voluntary movements where your eyes will jump from one point to point (ie: scanning a picture)
2. Vestibulo-occular Reflex
a. Uses the vestibular system in the event that the head is spun rapidly
b. Keeps the eyes in position of your former point of fixation
3. Optokinetic Reflex
a. Utilized in a situation such as watching the landscape pass rapidly while in a train
b. Eyes move rapidly to keep the object of focus in the center of the visual field for as long as possible
NON-CONJUGATE EYE MOVEMENTS (eyes move in different directions)
1. Vergence
a. Convergence and Divergence: eyes move away or toward each other
2. Dysconjugate Gaze
a. A pathological movement pattern; eyes move erratically and totally independent of one another
SR
LR6(SO4)3
Clinical Correlations
1. H-Test
a. Used to test each of the extraocular muscles
b. See explanation of use on page 1, under extraocular muscles
2. Trochlear Nerve Palsy (CN-4)
a. Eye will deviate up-and-in in light of the unopposed Inferior Oblique
3. Occulomotor Nerve Palsy
a. Loss of MR, SR, IR and IO
b. Eye will deviate down-and-out due to unopposed LR and SO function
4. Abducens Nerve Palsy (CN-6)
a. Eye will deviate medially due to unopposed action of the Medial Rectus
5. Diplopia
a. Basically, caused by the fact that the image is
landing on different points on the visual field
for each eye because one eye is unable to focus
the image properly on the fovea
b. Therefore, when info gets relayed to V1, it is
registering as actually existing in two places in
space thus causing double vision
RED GLASS TEST
c. Holding a red glass over the right eye (Red and
Right) the patient looks at a white light
d. Normal People the image from both eyes will
match and merge properly in the cortex thus creating a Pink light (combining the red and white)
e. Mismatch the images do NOT match which creates two individual lights (white and red). The light
perceived to be in the center of the visual field will define the good eye and the light perceived to be in the
periphery will define the bad eye and the direction of the pathologic gaze
6. Internuclear Opthalmoplegia
a. Based on a lesion of the MLF which if lost (think of saccadic eye movements) the abducens nucleus will
not be able to transmit info to the oculomotor nucleus (CN-3) so the ipsilateral MR is unable to respond
7. PPRF Lesion
a. Will result in inability to trigger ipsilateral abducens nucleus, resulting in inability to activate the
ipsilateral CN-6 and inability to initiate and send info up the MLF (even if the MLF is intact) thus losing
CN-4 as well
30 Vestibular System
Hair Cells
The receptor cells of the vestibular and cochlear division of the inner ear
Responsible for transducing mechanical stimuli into neuronal stimuli onto the
afferent fibers of CN-8
The apex of the hair cell contains stereocilia which is surrounded by endolymph
o The endolymph has a very high K+ concentration which is essential for
the signal transduction process
CN-8
1. Depolarization of Hair Cells
a. Mechanical force from the endolymph against the hair cells (as seen in
the picture) will open or close the TRPA-1 channels causing either a depolarization or hyperpolarization
b. The tip-link between the stereocilia directly opens the hatch on top of the TRPA-1 channels causing
potassium influx that will depolarize the hair cell (these depolarizations are graded in the hair cell)
c. The depolarization of the hair cell (due to K+ influx) will open Calcium-gated channels
d. The influx of Ca2+ will cause the NT release on CN-8 causing a full Action Potential
i. The frequency of action potentials increases as the graded potential of the hair cell increases
Neutral
Depolarization
Hyperpolarization
2. Semicircular Canal
a. Endolymph filled pipes whos walls are also lined with hair cells
b. When the endolymph moves relative to the walls of the canals (a phenomenon seen when the head spins) it
causes the cilia of the hair cells to bend (causing depol/hyperpol) which deduces angular acceleration
EXAMPLE
c. the semicircular canal will rotate to the LEFT but the endolymphs inertia is delayed (think of how
the water in a rotating bucket takes time to reach the speed of the walls of the bucket)
d. this effect of the endolymph moving much slower than the wall, which has the hair cell attached to it, will
cause the cupula/cilia to bend to the RIGHT relative to the walls
e. depending on their orientation, this bending will either cause excitation or inhibition
B.
Vestibular Nystagmus
1. Nystagmus
a. Alternating smooth pursuit in one direction followed by saccadic movement in the other direction
i. Slow Phase driven by reflex circuitry
ii. Fast Phase simply the reset mechanism driven by the saccadic circuitry
b. Note that there is a difference b/w physiological and pathological nystagmus
2. Vestibulo-Ocular Nystagmus
a. Very simply, is a physiological nystagmus induced by continuous rotation of the endolymph
b. This endolymph flow then activates the VOR
c. This stimulus is persistent (as seen when spinning on a chair) thus the eyes keep flipping back and forth
d. Once the eyes reach a maximum gaze that is opposite to the direction of the head spin, the eyes quickly
reset and then continuously repeat this process until the person stops spinning
SUMMARY
1. the slow phase is the part where the eyes swing in the opposite direction of the head spinning
2. the fast phase is the part where the eyes reset after reaching maximum gaze and is driven by saccadic
circuitry (which was seen in lecture 28)
Clinical Correlations
1. Occulocephalic Maneuver (Dolls eye maneuver)
a. The examiner forcibly turns the head of the patient and looks to see if the VOR is intact
b. This should work on comatose pts as well
2. Caloric Testing of VOR
a. Place water in the ear of the patient which changes the density of the endolymph and induces a spin
b. COLD WATER makes the endolymph sink thus inhibiting that side which will cause a reaction as if the
head were spinning in the direction OPPOSITE to ear with the cold water
c. WARM WATER makes the endolymph float, this exciting that side which causes a reaction as if the
head were spinning in the direction toward the SAME SIDE of the ear with warm water
SUMMARY
I. C.O.W.S. Cold=Opposite; Warm=Same
II. The opposite and same refer to the spin of the head
3. Menieres Disease
a. Abnormalities of endolymph circulation caused by dilation of the endolymph compartment and
degeneration of the hair cells.
b. Characterized by sudden and recurrent attacks of vertigo
4. Motion Sickness
a. Caused by a discrepancy between the vestibular and visual inputs
5. Alcohol Intoxication
a. This is commonly known as the bed spins
b. The alcohol interacts with the endolymph and induces abnormal spinning of the endolymph similar to
that seen in the caloric testing of the VOR
6. Antibiotics (streptomycin)
a. Can be toxic to the hair cells; so take with extreme caution as they can accumulate in the endolymph
7. Pathological Vestibular Nystagmus
a. Can be caused by damage to one side of the vestibular system (either the canals or CN-8)
b. This will induce a slow phase toward the side with the damaged labyrinth and a fast phase toward the
normally functioning side
c. This nystagmus will persist as this pathological stimulus also persists
31 Ocular Reflexes
Optokinetic Reflex and Smooth Pursuit
Parieto-Occipital Eye
Field
1. Definition
a. The OKR involuntarily realign the point of
fixation during movement of the entire visual
field or an object within the visual field
2. Visual Information Processing
a. Look at the following diagram and note that
the Parieto-occipital eye field is exactly where
the Magnocellular parallel pathway lands and
remember that this dorsal path receives info for Motion
b. The parieto-occipital eye field is then responsible for forming the efferent limb of the OKR that triggers
the necessary eye movements
3. Pathway of the OKR
a. Efferent fibers begin at the parieto-occipital eye
field and descend to the Pontine Nuclei located
in the Pons
b. From the synapse in the Pons they cross the
Midline and synapse in the vestibulocerebellum
c. From the vestibulocerebellum they go to the
Vestibular Nucleus where fibers are then sent to
The Abducens Nucleus
d. From this point onward, the pathway has already
been seen when we studied saccadic eye
movements and consensual horizontal movement
Optokinetic Nystagmus
1. Natural Occurrence
a. This would happen if you were trying to follow the passing telephone poles outside while in a train
i. The Slow phase would be controlled by the OKR which as we know, attempts to keep the object
within the visual field
ii. The Fast Phase (reset) is driven by saccadic circuitry in the opposite direction
b. The OKR keeps the pole in focus until it reaches the limit of vision thereafter using saccadic reset circuitry
to catch the next pole
2. Rotating Chair Experiment
VESTIBULAR CONTRIBUTION
a. The start of the rotation will cause the endolymph to being flowing in the direction opposite of the spin
b. This will induce the VOR but for the first ~30seconds it will cause Vestibulo-Ocular Nystagmus
i. The Slow phase is in the opposite direction of the spin and driven by the VOR
ii. The Fast phase is in the direction of the spin and is driven by saccade
c. The Vestibulo-Ocular Nysagmus will continue until the endolymph is rotating at the same speed as the
head where it is at this point that the Vestibular system is no longer stimulated and the OKR takes over
OPTOKINETIC CONTRIBUTION
d. Very simply, once the vestibular system no longer receives stimulation (which happens at the point
where endolymph and head spinning are equal) the Optokinetic system takes over
e. The OKR needs only visual information, thus the physical movement of the head makes no difference
f. From this point on, Optokinetic Nystagmus will persist exactly as it was seen when it occurs naturally
RE- CONTRIBUTION FROM VESTIBULAR
g. At the point when the spinning is eventually stopped, the endolymph will again begin to flow relative to
the head, but now its in the opposite direction thus the VO-Nystagmus will ensue in the other direction
Corneal Reflex
Clinical Correlations
CN-7
CN-5
Spinal Nucleus
of CN-5
Left
Eye
Poke Cornea
1. General Info
a. Causes the eyelid to blink if something touches the cornea
b. The trigeminal nerve sends pain fibers to the brainstem
CN-7
which activates the efferent limbs of the blink reflex
2. Pathway
Right
a. CN-5 sends afferent pain stimulus from the cornea,
Eye
entering at the Pons and then it is sent down to
synapse in the Spinal Nucleus of CN-5 (blue)
b. Smaller fibers leave the spinal nucleus of CN-5
and ascend to the Facial Nucleus
Facial Nucleus
c. From the facial nucleus, efferent motor fibers are
sent to BOTH Orbicularis Oculi muscles via CN-7 (purple)
**Remember**
Orbicularis Oris (CN-7) closes the eyelid
Levator Palpebrae Superioris (CN-3) opens eyelid
1. Optokinetic Nystagmus
a. Can be tested using OKN tape or a spinning drum with stripes (or animals/figures for children)
b. Simply move the tape and in healthy ppl, OKN should be seen
i. If it is not seen, it may be due to damage to the parieto-occipital eye field
2. Pupillary Light Reflex Test
a. Use a penlight to elicit the reflex and see if there is pupillary constriction and if so, is it consensual
b. Stimulating each eye individually and looking for the reaction in both eyes will define exactly where the
lesion is (afferent or efferent) if there is a deficit
3. Corneal Reflex Test
a. Identical principle to the pupillary light reflex only the stimulus is direct tactile stimulation to the cornea
4. Bells Palsy
a. Is caused by a peripheral lesion to CN-7; often acute onset due to swelling/compression of the nerve at the
bony facial canal (think of how this affects the corneal reflex; eyelid and the nasolabial fold)
32 Auditory System
The Nature of Sound
GENERATED by mechanical vibrations that generate pressure waves in the medium they are traveling in
o High Pressure waves have a higher number of molecules per volume
o Low pressure waves are the opposite, with a lower number of molecules per unit volume
FREQUENCY is the tone or pitch and is measured in Hz (cycles per second)
o Humans can hear a frequency range of 20-20,000Hz
AMPLITUDE is the intensity or loudness measured in dB
o For example: normal breathing is ~10dB and a jet engine is ~150dB
The Cochlea
1. Fluid Compartments
a. The Scala Vestibuli and Tympani are continuous with
each other and are filled with perilymph which has an
ionic composition that is similar to ECF
b. The Scala Media is filled with endolymph and is high
in K+ due to secretions from the Stria Vascularis
c. The Basilar membrane separates the Media from the
Tympani and supports the Organ of Corti
i. The organ of corti contains the hair cells which
are bathed in the endolymph compartment and
is necessary because of the high K+ concentration needed by the hair cells for signal transduction
2. Traveling Waves in the Cochlea
a. Movement of the stapes produces pressure on the oval
window which moves the fluids within the cochlea
b. This movement of fluids (not compression) is best
described as traveling waves which are translated to the
basilar membrane as seen in the diagram
3. Basilar Membrane
a. Is base on a Place Code for sound frequencies which says the amount of deflection of the basilar
membrane is based on its mechanical properties at that particular point in the membrane
b. AT THE BASE
i. At the oval window, the basilar membrane is narrow and stiff, responding to HIGH frequencies
c. AT THE APEX
i. Near the helicotrema, the BM is wide and floppy therefore most responsive to LOW frequencies
d. ENVELOPE OF WAVES
i. Is the sum of the deflection of the BM at different stages of the travel of the wave; which as we
now know exhibits variations from base to apex
4. Inner Hair Cells
a. Responsible for signal transduction as seen in lecture 30
b. Traveling waves on the BM cause a deflection of cilia on
the hair cells that are attached to it
5. Outer Hair Cells
a. Responsible for amplifying the deflection of the basilar
membrane and therefore amplifying the output signal
b. The outer hair cells have motor proteins that cause them to shorten in the event of a depolarization
(which will happen if the cilia are deflected, similar to the inner hair cells)
c. If the shortening across many outer hair cells takes place in proper sync, they can help push and pull the
basilar membrane such that its deflection is maximized thus amplifying the outgoing signal.
Auditory Pathway
1. The Basics of the Auditory Pathway
a. Begins with the auditory portion of CN-8 and enters the brainstem at the level of the Ponto-Medullary
Junction
b. Fibers then synapse in the anterior and posterior Cochlear Nuclei then undergo extensive crossing over
until they reach the Primary Auditory Cortex (A1)
c. This extensive crossing over is why there are no lesions which produce unilateral hearing loss
i. This of course does not include the structures of the ear, CN-8 and the cochlear nuclei
2. Primary Auditory Cortex A1
a. Location
i. A-1 is located in Broadmann
Area 41 and 42 which comprise
the transverse temporal gyri
b. Tonotopic Organization
i. A-1 is organized by frequency
sensitivity along the rostro-caudal
axis as seen in the diagram
c. Columnar Organization
i. A-1 is organized in columns that
are grouped according to their
pattern of input
ii. EE columns are those that are Excited by both ears
iii. EI columns are those that are Excited by ONE ear and Inhibited by the OTHER ear
3. Input Layer IV
a. The primary auditory cortex, identical to the other primary sensory cortex areas, receive input from the
thalamus in layer-4 where the thalamo-cortical fibers synapse
Localization of Sound
1. Low Frequency Sound
a. Based on TIME; pressure waves from space will reach each ear at different times which is interpreted and
understood to come from the given location
b. The time delay is detected by the binaural pathways to the superior olive (MSO) by a mechanism known
as Coincidence Detection
i. If the EPSPs from each ear arrive at the superior
olive at the SAME TIME (coincidence) there
will be a large signal
ii. If the EPSPs from each ear arrive at the superior
olive at DIFFERENT TIMES (no coincidence)
there will be a smaller signal
c. The timing of EPSP arrival and signal size gives the
understanding of where the sound is coming from
2. High Frequency Sound
a. Based on AMPLITUDE/INTENSITY
b. The amplitude varies based on the sound shadow created by the head if the source is lateral to the midline
c. The amplitude received by one ear is dampened by the head causing a lower amplitude and a lower
signal versus the other ear who receives a signal without any dampening thus a higher signal
INTERPRETATION
d. Fibers from one ear synapse in the ipsilateral superior olive as well as collaterals to the Trapezoid nucleus
i. The ipsilateral superior olive sends the output info to the cortex
ii. The Trapezoid nucleus sends inhibitory fibers to the contralateral superior olive
iii. Thus, the superior olive on each side has direct excitation ipsilateral and indirect inhibition from
the contralateral side
e. The sum of the inputs at the superior olives result in contralateral inhibition and ipsilateral excitation as
seen in the schematic
i. If one side starts off with an intrinsically higher intensity, its inhibitory contralateral will
hyperpolarize the opposite superior olive
3. Summary of Localizations
a. LOW FREQ in the medial part of the superior olive, using coincidence detection
b. HIGH FREQ in the lateral part of the superior olive, using interaural amplitude differences
Clinical Correlations
NEUROLOGIC TESTING
1. Webers Test
a. Place the tuning fork on the forehead and see where the sound is louder, right or left?
b. Normally, the person should say it is equal
c. Conductive Problem sound lateralized to the AFFECTED side (ipsilateral)
d. Sensorineural Problem sound lateralized to the UNAFFECTED side (contralateral)
2. Rinnes Test
a. Now that we know which side has a problem, the Rinnes test will tell us what kind of problem we have
b. The tuning fork is places on the mastoid process and held there until the patient no longer hears the sound
as it travels thru bone
c. Once the patient states they no longer hear it (via bone), the fork is held in the air next to the ear
d. Normal the air conduction should last longer and is louder due to amplification mechanisms utilized in
air conduction
e. Conductive Hearing Loss diminished air conduction; thus bone conduction is better and we now know
that this is a problem with the conductive system and not the neurologic system
DISORDERS
1. Otosklerosis
a. Fusion of the bony labyrinth (stapes to oval window) causing Conductive hearing loss of up to 40dB
2. Vestibular Schwannoma
a. Tumor of Schwann cells in vestibular division of CN-8 causing Sensorineural hearing loss
3. Loss of Hair Cells
a. Can also cause Sensorineural hearing loss
b. May be due to aging or the exposure to high frequencies (+100dB)
c. This loss cannot be replaced by cell division
4. Cochlear Implants
a. Consists of a microphone, electronic processor and many stimulating electrodes in the cochlea to help
restore hearing
b. The apparatus delivers sound directly to the cochlear nerve in the event that the hair cells are
damaged/lost
33 Chemical Senses
The Gustatory System
1. Basic Taste Qualities
a. Salty sodium chloride
b. Sour acids and hydrogen ions
c. Sweet sugars (ie: sucrose)
d. Bitter toxic or poisonous components
2. Taste Bud Receptor Cells
a. The apical pole nearest the pore, is the site of
signal transduction
b. The basal pole is the site of transmitter release
onto afferent fibers
c. Basal cells, located at the basal pole, are able to differentiate into new taste receptor cells
Gustatory Pathway
The gustatory pathway does NOT cross the midline, thus it is a completely IPSILATERAL tract
1. Innervation of the Tongue
a. Anterior 2/3rd Facial Nerve (7)
b. Posterior 1/3rd Glossopharyngeal Nerve (9)
c. Most Posterior including the Glottis Vagus Nerve (10)
2. Pathway
a. The primary afferent nerve is either CN-7,
CN-9 or CN-10 which are all psuedounipolar
neurons with their soma in the respective
ganglia (Geniculate, Inferior Glossopharyngeal
or Inferior Vagus Ganglia, respectively)
3. Signal Transduction
a. Is done solely by a Metabotropic cAMP pathway
b. The cAMP will open the cation channel allowing both Ca2+ and Na+ inside simultaneously that will cause
the depolarization of the olfactory receptor neuron
4. Odorant Receptors
a. Each receptor neuron expresses one of the 1000 different receptor proteins sensitive to a single odorant
b. Because we are sensitive to tens of thousands of odorant molecules and there are only 1000 proteins, it is
clear that we use these in multiple combinations to interpret and understand such an array of smells
i. ie: one odorant stimulates multiple receptor neurons at varying degrees to define specific odors
5. Olfactory Bulb and Pathways
a. Vertical information passes from the olfactory
receptor neuron, thru the cribriform plate and to
the bulb
b. Horizontal information exists similar to that seen
in the retina, where these inhibitory interneurons
assist in segregating the vast number of odorants
into individual smells based on the combination of
levels of excitement of each receptor type
Clinical Correlations
LOSS OF TASTE FUNCTIONS
1. Hypogeusea
a. Decreased taste function usually due to oral cavity pathology (secondary to salivary gland dysfunction)
leading to taste bud destruction
2. Ageusea
a. Total loss of taste function may be due to lesion on Chorda Tympani (CN-7)
b. Usually in conjunction with Bells Palsy (CN-7); causing ipsilateral taste loss to anterior 2/3rd of tongue
c. Can also be due to Wallenbergs Syndrome (lateral medullary syndrome) due to an infarction of the lateral
medulla caused by an occlusion to the PICA
LOSS OF SMELL FUNCTIONS
1. Hyposmia
a. Decreased smell function (is more common than hypogeuse) where the pt complains that they cant taste
anything but it is usually an inadequate taste because of the loss of the smell of the food
2. Anosmia
a. Total loss of smell most likely due to compression of the olfactory tract by tumors, particularly
meningiomas
3. Olfactory Hallucinations
a. Partical epileptic seizures originating in the vicinity of the uncus will commonly induce olfactory
hallucinations of pungent and unpleasant smells but they do not actually exist
Lateral Paths
Flexor Bias
Medial Paths
Extensor Bias
Clinical Correlations
1. Amyotrophic Lateral Sclerosis (Lou Gehrigs Disease)
a. Progressively weakens and later destroys LMNs
b. It will eventually effect parts of the pyramidal tracts and precentral gyrus
c. Loss of respiratory function eventually causes death
d. Patients often within 3-5 years of Dx
2. Spinal Cord Diseases
a. Usually affect motor and somatosensory tracts in the white matter
b. May also affect motor neurons of anterior horn and sensory neurons of dorsal horn
3. Anterior Spinal Artery Syndrome
a. Caused by an infarction to the Anterior Spinal Artery which supplies circulation to the anterior 2/3rd of
the spinal cord (as seen in x.s.)
b. This will compromise:
i. Second order motor neurons in anterior horn
ii. Lateral & Anterior corticospinal tracts
iii. ALS sensory system
c. This will result in:
i. Spastic Paraparesis and/or
Paraplegia (anterior horn damage LMN)
ii. Bilateral loss of TP below (ALS remember lissauers)
iii. TVP intact
iv. Urine retention and sexual dysfunction
4. Central Medullary Syndrome
a. Most likely caused by Syringomyelia
b. Typically causes segmented muscle atrophy (usually hands and fingers)
c. Loss of TP
d. See lecture 23 for more details
Paraplegia
Paraplegia
1. Trauma
a. Often a result of trauma causing a BILATERAL impairment of
the spinal cord
b. Cells of the long tracts are cut or crushed contusion, compression or laceration
i. Note this is an UPPER Motor Neuron impairment
2. Symptoms
a. Flaccid paralysis below the lesion (spinal shock) followed by
development of spasticity
b. Increased deep tendon reflexes and clonus
c. Positive Babinski reflex
d. Urine retention, painless bladder distention and overflow
e. Decrease of flexor spasms several months after injury
f. Loss of ALL Somatosensory below
Corticobulbar Tract
Bulbus = Brainstem
Corticobulbar fibers innervate motor cranial nerve nuclei where their route depends on the CN being innervated
Corticobulbar Fibers to Hypoglossal Nucleus
a. Central (Upper) Lesion
i. Will cause contralateral denervation of the tongue
b. Peripheral (Lower) Lesion
i. Will cause ipsilateral denervation of the tongue
MLF
Clinical Correlations
1. Decorticate Posturing
a. A lesion ABOVE the Red Nucleus impairing Corticorubral and Corticospinal fibers
b. The Red Nucleus is actove but there is NO cortical input
c. ARMS FLEXED
i. flexion due to most powerful Rubrospinal influence
d. LEGS EXTENDED
i. Extension by unopposed Pontine Reticulospinal and Vestibulospinal due to the fact that the
Rubrospinal intrinsically has little influence and the other flexor being the Corticospinal tract is
interrupted by the lesion
2. Decerebrate Posturing
a. A lesion BELOW the Red Nucleus impairing Corticospinal/bulbar/rubral Tracts
b. All flexors across the body are blocked/impaired thus, all extensors act unopposed.
Muscle Spindle
1. What are they?
a. Encapsulated structures found in most skeletal muscles used to monitor its length
b. The number of spindles in the muscle is directly related to the muscles function
i. Muscles involved in fine movement (hand) have more spindles than coarse moving muscles (back)
2. Components of the Spindle
a. Small group of 2-12 intrafusal () fibers central regions are non-contractile
b. Large diameter myelinated sensory axon (1a-axon) with sensory ending in the intrafusal belly
c. Small diameter myelinated motor axon that innervate the distal contractile regions (gamma-motor ending)
INTRAFUSAL FIBERS
3. Intrafusal Fibers
a. Lie w/in the spindle between/parallel to the
extrafusal fibers and are attached to the muscles
tendons
b. When the muscle contracts, the muscle shortens
and 1a firing rate
c. When the muscle stretches, 1a firing rate increases
4. THREE Types of Intrafusal Fibers
a. Dynamic Nuclear Bag Fibers sensitive to length
change & rate of change
b. Static Nuclear Bag Fibers sensitive to length change ONLY
c. Nuclear Chain Fibers sensitive only to length change ONLY
5. Innervation of Intrafusal Fibers
SENSORY INNERVATION
a. Group 1a is the primary sensory ending carrying STATIC & DYNAMIC (length and rate) afferents
b. Group II secondary ending carrying STATIC ONLY
MOTOR INNERVATION
c. A-Gamma small myelinated and low velocity axons carry motor innervation to the intrafusal fibers
**note that the A-Alpha fibers are responsible for the motor innervation of the extrafusal fibers**
Muscle Efferents
1. Two Types of Motor Neurons
a. A-alpha large, myelinated, high velocity passing via ventral horn to limb muscle Extrafusal fibers
b. A-gamma small, myelinated, lower velocity passing via ventral horns to limb muscle Intrafusal fibers
2. In the Spinal Cord
a. These alpha and gamma motor neurons are both located in the ventral horn of the cord
b. RENSHAW CELLS
i. Are inhibitory interneurons of the anterior horn that receive collaterals from the alpha motor
neuron and work to avoid damage in the event of excessive contraction (like golgi)
c. Spatial Distribution distal-proximal rule (see lecture 40)
Renshaw Cells
Motor Unit
1. Motor Unit
a. Includes the motor neuron and the muscle directly activated by it
2. Motor Nuclei
a. Consist of 100 motor neurons (on average) to control a typical muscle
b. They congregate to create this motor nucleus in the anterior horn of the spinal cord as well as the
brainstem for motor CNs
3. Distribution
a. A motor axon branches at its muscle and each fiber receives only one ending of the branching
b. The NMJ is located in the center of the muscle fiber and is where APs are generated
c. The number of muscle fibers in a motor unit decreases with increasing fine motor control
i. ie: muscles of the hand are about 10 fibers per unit where the back muscles are ~1000 fibers/unit
4. Three Types of Motor Units
a. Type I Slow-twitch muscle fibers; low tension; fatigue resistant; aerobic; innervated by relatively small
motor neuron and axon
b. Type IIA Fast fatigue-resistant (almost); large tension; some aerobic capacity; innervated by relatively
large motor neuron and axon
c. Type IIB Fast fatigable; large tension; anaerobic; innervated by relatively large motor neuron and axon
5. Factors Controlling Contraction
a. The force developed by the muscle fibers increases with increasing firing rate of the motor neuron
b. The force will also increase as more motor units are recruited to the excited state
Clinical Correlations
1. Hypotonia
a. Reduced muscle tone (atrophy) due to damage to either the 1a afferent or the alpha motor efferent
2. LMN Syndrome
a. Caused by destruction of the motor neuron in the anterior horn, the axons in the ventral roots or the
peripheral nerves
b. This can cause:
i. Atrophy
ii. Loss of voluntary and reflex responses
iii. Hyporeflexia
iv. Fasciculations and Fibrillations
NMJ Impairments
1. Botulism
a. Toxin of an anaerobic bacteria which stops ACh vesicles from docking at the NMJ
b. This will inhibit ACh exocytosis, resulting in paralysis
c. THREE WAYS TO BE INFECTED
i. Eating food containing botulism toxin
ii. Wound infected with Colostridium botulinum
iii. Ingesting spores of Colostridium botulinum
2. Alpha-Latrotoxin
a. BLACK WIDOW massive ACh release
b. Travels via lymph to the blood causing tetanus, painful muscle contraction and eventual paralysis
3. Beta-Bungarotoxin
a. OTHER SNAKE VENOM reduces ACh release by acting on exocytosis
4. Curare (turbocurarin)
a. ARROWHEAD POISON found in plants and is a reversible nAChR antagonist temporary paralysis
5. LAMBERT-EATON SYNDROME
a. Autoimmune against votage-gated Ca2+ channels which causes an insufficient release of ACh
b. Continued contractions will cause an [ACh] in the cleft until it reaches a concentration sufficient to elicit
an proper contraction
c. Often associated with Oat Cell Carcinoma of the lung
d. SIGNS & TESTS
i. On examination, weakness improves with activity
ii. Decreased reflexes
e. THERAPY
i. Remove underlying tumor and give Immunosuppressive drugs
ii. Calcium gluconate to enhance Ca2+ influx
iii. 4-AP will block K+ channels that increases presynaptic impulse duration causing Ca2+ release and
eventually improve ACh release (as acetylcholine release is Ca-dependant)
LMN Syndrome
1. What is it?
a. Second order neurons which stimulate the muscle are lost
b. The lesion is either on the motor axon or at the soma in the spinal cord or brainstem (CNs)
2. Causes
a. Viral Infection Poliomyelitis
b. Trauma
c. Neuro-degeneration
3. Sx/Sx
a. Weakness/paralysis
b. Loss of reflexes
c. Fasciculations
i. Irregular spontaneous contractions giving visible twitches
ii. Alone, is not a sign of motor neuron damage but together with fibrillations denotes denervation
d. Fibrillations
i. Spontaneous contractios of a single muscle fiber
ii. As the muscle becomes denervated, the fetal type nAChR spreads across the entire muscle fiber
iii. They now are hypersensitive to cations as more Na and Ca channels are inserted
e. Atrophy
POLIOMYELITIS
Poliovirus can affect the whole body but most cases the motor neurons in the ventral horns
Severe cases causes permanent paralysis or death
Transmission person-to-person contact (nose, mouth and fecal)
Prevention polio vaccine (90% effective)
43 PNS Disorders
Signs of PNS Lesions
1. Negative Signs loss of normal function
a. Muscle Weakness
b. Loss of Reflexes
c. ANS deficit (no sweat)
d. TP loss/impairment
Regeneration/Regrowth in PNS
1.
2.
3.
4.
Peripheral Neuropathy
GUILLIAN-BARR SYNDROME
1. Demyelination of peripheral axons which begins several weeks after viral respiratory/GI infection
2. This is most likely due to an autoimmune response
3. Respiratory support is often needed until the Schwann cells can successfully re-myelinate the nerves
4. Normally, patients are able to recover from this syndrome
5. Treat patients with IV immune globulin
LEPROCY (Hansens Disease)
1. Caused by Mycobacterium Leprae
2. Characterized by skin lesions and profound sensory loss (TP) due to ischemia/compression of peripheral axons
3. The infection will also cause muscle weakness
4. Antibiotic treatments are successful
DIABETES MELLITUS
1. Usually seen in insulin-dependent diabetics
2. Will cause:
a. Autonomic Neuropathy
b. Motor Neuropathy
i. Usually asymmetric
c. Sensory Neuropathy
i. are usually symmetric and affect unmyelinated axons carrying TP in a stocking distribution
ii. unmyelinated axons and DRG cells are very vulnerable to hyperglycemia
iii. this may be due to a lack of nutrient and protein supply to distant parts (cytoskeleton problem)
ALCOHOLIC POLYNEUROPATHY
1. Caused by neurotoxic effects of alcohol-associated malnutrition (Vitamin B1Thiamin deficiency)
2. Starts with sensory loss in lower legs and progresses to motor losses in the legs
3. Nerve conduction velocity is usually normal
4. 10+ yrs of alcoholism establishes high risk
LEAD POISONING
1. Children are more susceptible because their brain and CNS are not fully developed
2. May lead to enecephalopathy, IQ, learning deficits, mental retardation, coma and death
3. Weakness in distal muscles more than proximal
4. Focal weakness in finger extensor muscles
5. Bilateral arm weakness and wasting/atrophy in chronic conditions
6. ADULTS causes memory and concentration problems as well as motor peripheral neuropathy
7. Virtually NO SENSORY SYMPTOMS
44 Spinal Reflexes
Reflexes
DEFINITIONS
LANDMARKS FOR REFLEX TESTING
1. Monosynaptic/Deep Tendon/Myotactic Reflex
a. afferent and efferent limbs are directly
connected (ie: ONE single synapse)
2. Polysynaptic Reflex
a. Afferent and efferent limbs are connected
by ONE OR MORE interneuron
3. Reflex Arc Components
a. Sensory receptor (spindle/golgi tendon)
b. Afferent neuron
c. Synapse on efferent (LMN) neuron
d. Muscle contraction
4. Types of Stretch Reflexes
a. Deep Tendon Reflex
b. Golgi Tendon Reflex (inverse myotactic)
c. Flexion Crossed Extension Reflex
5. Afferent Limbs
a. Spindle 1a fibers
b. Golgi Tendon 1b fibers
SCALE FOR REFLEX SCORING
4 very brisk, hyperactive, with clonus
3 brisker than average (high normal)
2 average (normal)
1 somewhat diminished (low normal)
0 no response
Stretch Reflex
1. Basic Reflex Arc
a. Is in response to passive muscle stretching
b. 1a-fibers from spindle directly stimulate
alpha-motor fiber to contract the stretched
muscle
c. 1a-fibers also stimulate inhibitory
interneurons that eventually inhibit the
alpha-motor neuron on the antagonist
muscle
2. Negative Feedback Loop
a. The stretch reflex works as a negative
feedback loop to maintain muscle length
at a desired value
3. Gamma-motor Neuron
a. Are responsible for contracting the ends of the muscle spindle to keep its length identical to the muscle
fibers in an effort to maintain monitoring of the muscle length at all times
b. Posture via the patellar tendon and the quadriceps muscles. When the muscle relaxes,
there is less tension and the inhibition is removed. The muscle will then contract to
maintain proper posture
Flexion & Flexion Crossed Extension Reflex
1. Flexion Reflex Withdraw Reflex
a. In response to painful stimuli, causing rapid flexion
as a protective mechanism
b. Pain afferents (A-delta and C-fibers) will stimulate
excitatory interneurons that synapse on alpha motor
neurons to flex the necessary muscle
2. Flexion Crossed Extension Reflex
a. The Flexion Reflex is often associated with this Flexion
Crossed Extension Reflex in the contralateral limb
b. This will support the contralateral leg to maintain balance
if the flexion reflex causes the ipsilateral leg to lift when
you step on a pin
c. SUMMARY
i. Ipsilateral flexor stimulation and extensor inhibition
ii. Contralateral flexor inhibition and extensor stimulation
Clinical Correlations
Hyperreflexia: is an UMN lesion in the cortex or somewhere in the Corticospinal tract (develops after spinal shock)
Spinal Shock: Acute damage to the cord causing immediate areflexia caudal to injury; reflexes return in weeks
Hyporeflexia: diminished reflex caused by LMN lesion, NMJ/muscle disease, sensory loss or peripheral nerve lesion
Motor Loop
The Motor Cortex, Basal Ganglia and Thalamus are interconnected and form the MOTOR LOOP
GABA blue
o Inhibitory Effect
Glutamate red
o Excitatory Effect
Dopamine purple
o D1 Excitatory
o D2 Inhibitory
1. Inhibition from Basal Ganglia
a. Most neurons in the BG are inhibitory
as seen with the various GABA synapses
as well as some Dopamine Synapses
2. Substantia Nigra Pars Compacta
a. SNc neurons are dopaminergic and produce neuromelanin as a byproduct of dopamine metabolism
b. Degeneration of these dopaminergic cells are evident in autopsy as loss of the dark pigment neuromelanin
3. Striatum Dopamine Receptors
a. D1 receptor excitatory; mediating facilitation of striatum firing rate
b. D2 receptor mediates inhibition
c. These effects combine to reduce the tonic inhibitory output from the basal ganglia onto the thalamus
Area 6
Striatum
Thalamus
Spinal Cord
KEY:
Direct
Indirect
Inhibitory
GPe
GPi/SNr
Substantia Nigra
SNc
Parkinsons Disease
MOTOR COREX
1. Etiology
a. BILATERAL Degeneration of dopaminergic cells in the SNc
b. This will cause overactivation of the inhibitory effect of
the indirect pathway
c. This will also cause an underactivation of the excitatory
effect of the direct pathway
d. OVERALL excessive inhibition, hence a
hypokinetic disorder
2. Symptoms
a. The Sx/Sx are exhibited bilaterally as degeneration is bilateral
b. Akinesia absence or poor movements
c. Bradykinesia abnormal slowness of movements
d. Resting tremors
e. Muscular Rigidity
Lower
Motor
Neurons
D1
SNc
Thalamus
GPe
STN
GPi/SNr
Huntingtons Chorea
MOTOR COREX
1. Etiology
a. BILATERAL degeneration Strial neurons (with D2 receptors)
b. This will cause a loss of any and all control between the
Striatum and the GPe
Striatial Medium Spiny
c. This results in a loss of the inhibitory effect from the indirect
Neurons
pathway hyperkinetic disorder
i. The GPe will inhibit the STN on its own (in the
D2
D1
absence of striatal control)
ii. The STN now being inhibited, will not stimulate
the GPi/SNr to inhibit the thalamus
SNc
iii. The loss of inhibition onto the thalamus causes
excessive motor activity
GPe
2. Symptoms
a. Irregular BILATERAL movements
b. Dyskinesia excessive motor activity
STN
GPi/SNr
c. Involuntary movement of head, arms and legs
d. Marked change in mental status dementia and psychological/psychiatric troubles
Thalamus
MOTOR COREX
Hemiballismus
1. Etiology
a. Lesions of the STN usually arising from stroke
b. Causes underactivity of the indirect pathway on one
side of the midline
c. Loss of indirect pathway leads to loss of inhibition
causing excessive movement hyperkinetic disorder
2. Symptoms
a. This leads to irregular movements of the limbs and trunk
on the contralateral side
b. Characterized by involuntary flinging of the arms and
writhing movements of the leg ON ONE SIDE
Lower
Motor
Neurons
Lower
Motor
Neurons
D1
SNc
Thalamus
GPe
STN
GPi/SNr
The origin of the disease is genetic and to date, there is NO successful therapies to delay or slow its progression
Antidepressants are useful in managing clinical depression caused by HD
HYPOTHALAMUS
The control center for the most basic life processes; receive info from two major systems
Neuronal Input
o Visceral afferent sensory info enters CNS via spinal nerves to the hypothalamus
o May also enter via cranial nerves but it will stop in the solitary nucleus of brainstem before hypothalamus
Humoral Input
o Received thru circumventricular organs in the walls of the ventricles which contain fenestrated capillaries
o Lack of BBB detect chemical changes in blood and relay the info to the internal regulatory system
ANTAGONIST SYSTEMS
Consists of the sympathetic and parasympathetic divisions
Clinical Correlations
1. Pharmacological Influence of Autonomic Function
a. Directed toward the receptors on the target organ
b. Side effects are avoided by ensuring specificity
for the specific type/subtype of adrenergic receptor
c. Some examples are seen in the diagram
2. Hirschsprungs Disease Megacolon
a. Congenital absence of motility and peristalsis of the distal colon
b. This is caused by the absence of parasympathetic terminal ganglia in the distal colon
c. Feces is trapped and causes abnormal dilation, hence megacolon
3. Complex Regional Pain Syndrome
a. Chronic neuropathic pain syndrome follows injury to bone, soft tissue or nervous tissue
b. Pain persists after apparent healing is complete
c. Caused by an increase of sympathetic activity or sensitivity of nociceptors to NE
d. Increased sympathetic activity may also cause excessive sweating
CORONAL VIEW
1. Periventricular Zone adjacent to the 3rd Ventricle
2. Medial Zone contains most of the distinct nuclei of the hypothalamus
3. Lateral Zone contains less defined nuclei but is rich in fiber tracts
which connects the hypothalamus to other areas of the brain
SAGGITAL VIEW
Also see figure 2-28 in
the Haines Atlas; all
structures seen in this
diagram should be
familiar
Hypothalamo-Adenohypophyseal Pathway
1. Hypothalamic Control of the Anterior Pituitary
a. Parvocellular neuroendocrine cells from the Parvoventricular
and Arcuate nuclei terminate in the primary capillary
plexus of the superior hypophyseal artery in the infundibulum
b. Neuroendocrine substances are released into the primary
capillary plexus which drains into the portal vein
c. The portal vein then leads the blood flow toward the
anterior pituitary and into a second capillary plexus
d. Neurohormones controlling the anterior pituitary will
either induce or inhibition hormone release from the AP
2. Regulatory Hypothalamic Hormones Anterior Pituitary
a. Following hypothalamic stimulation, the
AP may release TSH,ACTH, LH, FSH,
GH or Prolactin
b. Of course, the AP hormone release depends
on the hormone released by the hypothalamus
c. The MOST IMPORTANT is the response to
stress where CRH causes a release of ACTH
which acts on the adrenal cortex to release the
stress hormone Cortisol into the blood which
acts on various target cells
Hypothalamo-Neurohypophyseal Pathway
1. Hypothalamic Control of the Posterior Pituitary
a. Magnocellular neuroendocrine cells from the
paraventricular and supraoptic nucleus send axons
directly to the posterior pituitary so called the
supraoptico-hypophyseal tract
b. These neuroendocrine cells release their
neurohoromone into capillaries of the inferior
hypophyseal artery thus entering the circulation
c. These neurohormones now in the blood can reach
their target tissues via the circulation
Clinical Correlations
1. Ventromedial hypothalamic Syndrome (Frohlich Syndrome)
a. Disorder of caloric balance causing obesity attributed to damage of the ventromedial nucleus
2. Diabetes Insipidus
a. Absence of ADH causes excessive thirst and urination (10L/day)
b. This may be due to a lesion of the supraoptic or paraventricular nuclei somewhere in PP the tract
3. Hypothermia
a. May be due to lesions of the posterior hypothalamus leaving the anterior hypothalamus unopposed
b. This causes: MR and vasodilation resulting in a body temp
4. Hyperthermia
a. May be due to lesions of the anterior hypothalamus leaving the posterior hypothalamus unopposed
b. This causes: MR, shivering and vasoconstriction resulting in a body temp
Clinical Correlations
1. Horners Syndrome
a. Unilateral Myosis, Ptosis and Anhydrosis due to underactive ipsilateral sympathetic outflow
b. Caused by:
i. Lesion/transcetion of the hypothalamospinal pathway (in the cervical region)
ii. Preganglionic lesion (on the chain)
iii. Postganglionic lesion at the level of the internal carotid (tumor in cavernous sinus)
2. Automatic Bladder
a. Some patients with a transection of the spinal cord will regain sacral reflexes
b. In this case the reflex to empty the bladder recovers and when the bladder reaches threshold, the reflex
response will spontaneously empty the bladder
3. Atonic Bladder
a. Dorsal nerve root lesions interrupt afferent sensory fibers making the pt lose the sensation of fullness
b. As the bladder fills, a constant dribbling will occur
4. Jet Lag
a. Dark/light cycle no longer parallels the endogenous circadian clock system typically causing temporary
insomnia which is sometimes treated with mild doses of melatonin prior to falling asleep
5. Sleep/Wake Disorders in the Blind
a. Disorders of this nature are very common in their absence of visual input (zeitgeber)
b. Pacemakers are not entrained to social cues and suffer from sx similar to jet lag
6. Seasonal Affective Disorder (SAD)
a. Also known as winter depression changing mood and sleep patterns
b. Due to daylight changes and is treated with light therapy to suppress melatonin synthesis
INAH-3 is twice large in heterosexual males when compared to the INAH-3 of homosexual males
This difference in size is seen to have an identical size variation between hetero- and females
Additionally the SCN is larger in homosexual males versus heterosexual males
Thus, this concludes that sexual orientation is linked to structural dimorphisms
Clinical Correlations
1. Fetal Exposure to Diethylsilbsetrol (DES)
a. Prenatal exposure during the critical period caused an enlarged SDN in females
b. The result was an increased occurrence of bisexual and homosexual girls DES Daughters
53 Consciousness
What is Consciousness?
DEFINITION
Awareness of ones self and ones place in the environment with the ability to respond appropriately to
environmental stimuli
CONSCIOUSNESS RESULTS FROM IMPORTANT FUNCTIONS OF THE BRAIN
Memory, learning, self from non-self and re-entry (where mechanisms located in thalamocortical system)
COMA
Non-sleep LOC lasting for extended period of time (unlike syncope)
LEVELS OF UNCONSCIOUSNESS
1. Lethargic pt can be fully aroused
2. Obtunded pt cannot be fully aroused
3. Stuporous sleep like status
4. Comatose no purposeful response
BRAIN STEM & CONSCIOUSNESS
1. Cells of the midbrain (reticular formation) receive ascending
info from the spinothalamic track and other
2. They are projected via 2 branches to higher cortical centers
a. To the thalamus activating and modulating
thalamic relay nuclei and intralaminar nuclei
b. To the lateral hypothalamic area which is joined
by ascending output from hypothalamic and basal forebrain cells
i. Lesions of either of these two branches, the thalamus, midbrain or cerebral hemispheres can impair
consciousness
c. The brainstem plays an important role for
i. Condition of consciousness, attentive vigilance and wake-sleep rhythm
EEG AND CONSCIOUSNESS
Thalamic relay neurons have two-physiological states
1. Transmission Mode wakefulness and awareness
a. Resting potential is near firing threshold
b. Cholinergic input from pons and basal forebrain is present
c. EEG shows desynchronized pattern low voltage and high frequency
2. Burst Mode deep sleep and coma
a. neurons hyperpolarized by inhibitory GABA from reticular formation input
b. EEG shows synchronized wave pattern high voltage and low frequency
Coma
1. Definition
a. A deep state of unconsciousness; unable to move or respond to environmental stimuli
b. Commonly caused by head injury or complications to another disease (ie: brain tumor or ICP)
c. Raw definition not opening eyes, not obeying commands and not uttering understandable words
2. Differentiation from Vegetative State Cortex/Higher Centers
a. A complete loss of higher brain function (cortex) however maintain breathing and circulatory functions
b. Spontaneous movements can occur such as eye opening to painful external stimuli but are unable to
respond to commands, to speak or respond meaningfully to environmental stimuli
c. Pt may cry, grimace or laugh but this is not the result of them interpreting and responding meaningfully.
No
response to speech/pain/etc
ii. Ischemia (vascular occlusion)
No
respirations
iii. Intracranial Hemorrhage
Pupils fixed/dialated
iv. Trauma
No VOR (cows/dolls eye)
v. Brain Tumors
No corneal reflex
vi. ICP and uncal herniation
4. Differentiation from Locked-in-Syndrome Pons
a. Blockage of basilar artery causing massive infarction to pons
b. Causes total paralysis of voluntary muscle except for vertical eye movement muscles and opening lid
c. Pts are fully aware but cant move and communicate via vertical eye movements and opening the eyelid
5. What Causes Coma
a. Supratentorial Mass Lesions
i. Epi/subdural/intracranial hemorrhage
ii. Cerebral infarc
iii. Brain tumor or abscess
b. Subtentorial Lesion
i. Brain stem infarc, tumor or hemorrhage
ii. Cerebellar hemorrhage or abscess
c. Metabolic & Diffuse Cerebral Disorders
i. Anoxia, ischemia, concussions, seizures, infection, subarachnoid blood
ii. Hypo/hyper glycemia, -natriemia
iii. Hypothyroidism, hypocortisolism, hypercarbia
iv. Drugs, liver failure, renal failure, sepsis,
52 Emotions
Theories of Emotions
1. James-Lange Theory
a. Emotional experience is induced by our somatic, autonomic and endocrine emotional expressions
b. we feel happy because we smile
c. New research shows that ppl who lack emotional experiences can still express emotions thus this is crap!
2. Cannon-Bard Theory
a. Emotional experiences (what we remember) triggers the emotional response of our body
b. our happiness makes us smile
Limbic System
1. Brocas Limbic Lobe
a. Consists of the Cingulate gyrus, Subcallosal gyrus, Isthmus,
Parahippocampal gyrus and Uncus
b. The term limbic system has developed to be synonymous
with the emotional system
2. The Papez Circuit
a. James Papez was first to note marked emotional outbursts
from patients with damage to their hippocampus and/or cingulate
gyrus
b. He created a mechanism of emotion based on his hippocampo-thalamo-cingulate-hippocampal circuit
now known as the Papez circuit
Clinical Correlations
1. Anxiety Disorders
a. Include panic disorders, OCD, PTSD, phobia and generalized
anxiety disorder
b. Attributable to an imbalance between the hippocamps (stress)
and the hippocampus (stress)
c. May also be attributable to an benzodiazepine receptors in
the frontal lobe
d. These findings define the key role of the amygdala as well as the i
nvolvement of other structures including the hippocampus,
hypothalamus and frontal lobe
2. Tumors
a. Temporal lobe tumors compromising the amygdala or its connections may lead to extreme aggression and
hostility
b. Tumors of the hypothalamus are often accompanied by spontaneous fits of anger or deep sadness
3. Psychomotor Epilepsy
a. Temporal lobe seizures with olfactory/gustatory hallucinations are followed by mood change (anxiety or
loneliness).
1. Language is Spontaneous
a. It does not need to be taught and emerges spontaneously
b. By this, it is distinguishable from writing/reading which does need to be explicitly taught
2. Thinking
a. It is NOT necessary for thinkning; while people do think in words, it is not necessary as ppl think in
images, abstract concepts and other non-linguistic forms
3. Lexeme
a. Different forms of a word that originate from one single word (ie: love loving, loved, etc)
4. Morpheme
a. Any word or word part that conveys meaning and which cannot be divided into smaller elements that also
can convey meaning
i. book is a morpheme; it cant be broken down further but books can be broken into book and s
5. Two Components of Language Design
a. WORD a combination between a sound and meaning
b. GRAMMER rules how lexemes are meaningfully combined
6. Morphology
a. Describes word structures and formation; combining word and affixes to larger words (adore able)
7. Syntax
a. Meaning sequence or order; describes how sentences are constructed and relations among words
8. Phonetics
a. Classification of sounds made in spoken language
b. Prosody describe the intonation, stress, rate, and rhythm, that provide speech with its melodic character
9. Production and Comprehension of Language
a. Production of a sentence
i. Choose words, grammatical rules to encode ideas and intentions and generate articulatory
commands in the motor system
b. Comprehension of a sentence
i. Coordinate sensory info from auditory (or visual) system with grammar and words and send the
info about interpretation to the memory and reasoning systems
ii. This takes a complex pattern of information flow to many parts of the brain
Development of Language
IN CHILDREN
1. Language development is spontaneous and the capacity to learn it is innate
2. The ability to learn language is due to the adaption of the human brain over evolution
3. Critical Time Markers
a. 5-7 months sounds
b. 7-8 months well formed syllables (ie: ma, da)
c. 1-2 years first word mama with an understanding of the connection between the word and their Mom
d. 2 years speaking in rich phrase (children language)
e. 3 years often correct use of grammar with a good understanding of the basic rules
IN HUMANS
1. Language most likely developed based on two parameters
a. Humans exploited the environment
b. Humans were involved in cooperation
2. Language has allowed for our ancestors to benefit from sharing acquired information
LANGUAGE PROCESSING
1. Incoming Spoken Word
a. Auditory signals auditory pathway primary auditory cortex
Wernikes Area elicitation of the words meaning in the area near Wernikes Area
2. Outgoing Spoken Word
a. Nonverbal meaning conversion to acoustic image in Wernikes Area arcuate fasciculus
Brocas Area motor cortex
3. Reading
a. Input from left visual cortex Wernikes Area elicitation of the words meaning near Wernikes Area
4. Writing
a. Non-verbal meanings conversion to a motor/visual image in Wernikes Area arcuate fasciculus
Brocas Area premotor area (above broca)
Aphasias
FLUENT APHASIA - Characterized by fluent speech with difficulties in comprehension and repetition
1. Wernikes Aphasia wernikes area (22)
a. Have no problem pronouncing/articulating words but have poor comprehension and repetition
b. This has been described as WORD SALAD
2. Transcortical Sensory Aphasia sensory assoc. cortex
a. Inability to speak spontaneously; comprehension deficits are present but REPETITION IS NORMAL
b. This is caused by a lesion of the sensory associated cortex; pts also have difficulty naming things
3. In Gerstmann Syndrome angular gyrus
a. Translation of visual patterns of letters & words into meaningful information is impaired
4. Conduction Aphasia arcuate fasciculus
a. Connection b/w Wernike-Broca is lost (arcuate fasicuclus) causing understanding without ability to repeat
b. The pt can say something wrong and realize it but when attempting to correct it, will repeat the mistake
Alexia
1.
2.
3.
4.
Dyslexia
Damage to the left hemisphere of the brain which leaves child unable
to perform proper word-identification when reading
These ppl have a problem with print-to-sound translation meaning they will read
the word cat as car
55 Mental Illness
STATISTICS
1. Symptoms
a. Impairment of cognition, emotion, thought, affect, perception, language and sense of self
b. Symptoms are acoustic, sometimes visual, olfactory, tactile or gustatory hallucination
c. TYPES OF SYMPTOMS
i. Positive addition of pathological symptoms
ii. Negative loss of normal function
iii. Disorganized disorder of thoughts, memory dysfunction and confusion
d. DISORGANIZED SPEECH
i. Frequent derailment or incoherence; word salad
e. GROSSLY DISORGANIZED or CAATONIC BEHAVIOR
i. Characterized by stupor/inactivity, mania and either rigidity or extreme flexibility
f. COGNITIVE SYMPTOMS
i. Disorganized/slow thinking, poor understanding, concentrating, expressing thoughts and memory
g. SOCIAL/OCCUPATIONAL DYSFUNCTION
i. Work, interpersonal relations and self care
2. Psychotic Episodes Include:
a. Social isolation/withdrawal
b. Odd behavior and impairment of normal responsibilities
c. Neglect of personal hygiene and a flat affet
3. Diagnosis
a. Exclusion of other diseases able to produce psychotic symptoms including
i. Encephalitis/meningitis
ii. Intoxication (amphetamins, PCP or diphenhydramine)
iii. Brain tumor
iv. Manic/Depressive illness
4. Prognosis
a. Generally poor; pts with negative symptoms have poorer prognosis
5. Pathogenesis
a. Genetic Aspect polygenetic (similar to HTN or diabetes)
b. Psychodynamic Aspect
6. Anatomical Abnormalities seen in pts with negative symptoms
a. Decreased blood flow to globus pallidus
(connection of basal ganglia to frontal lobe)
b. No increase in blood flow to frontal lobe
during memory tests
c. Thin cortex in medial temporal lobe and smaller
anterior hippocampus (defect in memory)
7. Treatment
a. Typical Antipsychotic Drugs High affinity to D2 receptors (see lecture 46)
i. Side-effects: blockage of D1 and D2 receptors
ii. Short-term effects: hand tremors and muscle rigidity
iii. Long-term effects: Tardive Dyskinesia; involuntary movements esp mouth and tongue
b. Atypical Antipsychotic Drugs High affinity to D3 & D4 receptors
i. Almost no side effects in the extrapyramidal system
c. All antipsychotic drugs have significant side effects and unfortunately do NOT treat the disease but only
help treat the symptoms
STATISTICS
DEPRESSION
1. Symptoms
a. Affect mood, body and thoughts and can continue for weeks, months or years
b. Persistent sad, anxious or empty; hopeless, helpless, worthless, guilty
c. Loss of interest in fun/pleasurable hobbies (incl. sex)
d. Decreased energy, fatigue/slowing down
e. Difficulty concentrating, remembering, decision making
f. Appetite changes; weight loss/gain
g. Suicidal thoughts/attempts
h. Persistent physical symptoms that do not respond to treatment; headaches, digestive disorders and pain
2. Causes
a. Genetic vulnerability based on family history
b. Additional factors include, stressed home/work/school
c. Stroke, MI, Cancer, Parkinsons and hormonal disorders can also cause depression
d. Death, relationship issues, financial hardship
e. Overall, it is the combination of biological, psychological and environmental factors
3. Pathogenesis
a. Genetic Factor polygenetic
b. Morbidity rate: higher in 1st degree relatives of pts with depressive illnesses
4. Types of Depression
a. Major Depression
i. Effect work, focus, sleep eating and enjoying pleasurable activities
b. Dysthymia
i. Less severe; no disabling long-term symptoms; generally not functioning well or feeling good
5. Treatment
a. Selective Serotonin Re-uptake Inhibitors (SSRI)
b. Tricyclic anti-depressives
c. Monoamine Oxidase Inhibitors (MAOI)
d. Electroconvulsive Therapy (ECT) severe/life threatening depression; Rx is ineffective; causes seizures
6. Prophylactic Treatment
a. Mood stabilizers include lithium, cabamacepine, lamotrigine, valoproate and others
BIPOLAR DISORDER aka Manic-Depressive Illness
Cyclic mood changes, swinging from severe highs (manias) and lows (depression)
Depressed Phase
o Patient has some or all of the symptoms of major depression
Manic Phase
o Overactive, over-talkative, excessive energy
o Pts judgment, social behavior are distorted and pt causes problems and embarrassment
o Pt feels elated, ideas of grandiosity and if not treated can develop into a psychotic state
MANIA
Exhibit sx such as excessive elation, irritability, decreased need for sleep, grandiosity, social inappropriateness
AFFECTIVE DOSORDERS: Findings In Functional Imaging
Area in pre-frontal cortex, below the genu in the corpus callosum
o Reduced activity during depressive phase and increased activity during manic phase
The sub-genual region of the prefrontal cortex is important for mood disorders and connects to many structures
involved in emotional behavior including:
o amygdala, lateral hypothalamus, nucleus accumbens and noradren/seroto/dopaminergic brain systems
56 Addiction
Dependence
DEPENDENCE SYNDROME
1. Based on the past year, three or more of these must be present
2. Considered a bio-psycho-social disease
Cause of Dependence
Risk factors are plentiful including neurologic developmental effects, social interactions, self esteem, family and many more
BIOLOGICAL/GENETIC FACTORS
Studies with twins from alcoholic families that are raised separately show definitive evidence for a greater likelihood for
developing alcoholism
Serotonin seems to be lacking (often genetic) with addicted people
SOCIO-CULTURAL FACTORS
1. Performance
a. Deadlines must be met, quantity of output predisposes for stimulants to work and sedatives to sleep
2. Consumption
a. Hunger satisfaction leads to excessive eating of different things and addiction of consumption (junk food)
3. Urbanization
a. Adaptation and dependence on technical environment
4. Mass Society
a. De-individualization leads to isolation and loneliness causing additive behaviors (depression=drugs)
5. There are many other to name but I think the point has been made
Effects of Drugs
Alcohol Detoxification
1. Withdrawl
a. As the body is accustomed to alcohol regularly, in the absence, the body exhibits withdrawal symptoms
making it exceedingly difficult to stop
2. Symptoms
a. Include: trembling, N/V, sweating, craving alcohol and in extreme cases, seizures
b. May also include tachycardia, hypertension and hallucinations
c. Last ~7 days
d. Delirium tremors (5% of pts) begin ~2-3 days after stopping and in extreme cases can be fatal
3. Detoxification
a. Most common Rx is benzodiazepines (valium)
b. Vitamin B1Thiamine
i. Thiamine is a co-enzyme needed to metabolize carbohydrates and without it can alter PPP and
cerebral energy metabolism
ii. Acute deficiency causes oculogyric crisis, ataxia and delirium similar to a diabetic coma
iii. Thus, giving glucose (D50) without thiamine can be very bad or fatal
Opiate Detoxification
2. Cold Opiate Detoxification
a. Symptoms present like GI-influenza
b. Non life threatening
c. Symptomatic Rx to combat
i. N/V/D, HTN & tachycardia
d. 2nd and 3rd days are the worst
e. No longer than 5-7 days
f. Hyposomnia can continue for weeks
Epilepsy
TYPES OF SEIZURES
1. Primary (idiopathic)
a. Result from constitutional or genetic disposition, where threshold for seizure is below normal
b. No aura or focal symptoms with both hemispheres involved which can be with or without convulsions
c. Petit mal absence seizure 10second absence of motor activity without postictal period to follow
2. Secondary (focal and symptomatic)
a. Result from known pathogenic lesion or disease process
b. May be intracranial or extracranial
c. May be a focal lesion or diffuse/generalized process or disturbance of brain function
3. Grand-Mal Seizure (tonic-clonic)
a. Characterized by LOC, falling to the ground and rhythmic convulsions
b. May be triggered by light, sound or touch
c. Tonic Phase
i. Muscle rigidity for ~20sec followed by the clonic phase
ii. Abrupt onset with grunt (tonic contraction of the diaphragm)
iii. Cyanosis may ensue due to poor respirations while actively seizing
d. Clonic Phase
i. Jerking of the extremities
e. Postictal Phase
i. Sleepy and disoriented, often with headache and muscle soreness
INTRACRANIAL VS. EXTRACRANIAL
1. Intracranial Causes
a. Primary Causes
i. Unknown (genetic or biochemical predisposition)
b. Secondary Causes
i. Tumor
ii. Vascular or Arteriovenous
iii. Trauma
iv. Infection
v. Ccongenital/hereditary disease
2. Extracranial Causes
a. Metabolic electrolyte, biochemical or inborn errors of metabolism
b. Anoxia
c. Hypoglycemia
d. Drugs
e. Drug or Alcohol Withdrawal
POSITIVE VS. NEGATIVE SYMPTOMS
1. Positive Symptoms
a. Sensory seeing light flashes, feeling fear, hearing noises or people talking
b. Motor jerking of arms, leg or face
2. Negative Symptoms
a. Sensory slowing of normal brain function and depression of consciousness
b. Motor Todd paralysis (postictal condition)
DIAGNOSIS
1. Diagnostic processes usually started after onset
of epileptic seizures
2. Tests include
a. Blood work, EEG, CAT/MRI/PET scans
b. Note that these tests can neither rule-out or
definitively diagnose epilepsy
TREATMENT
1. Anti-epileptic drugs are successful in approx
70% of patients in preventing or at least
reducing the frequency of seizures but they
do NOT cure the disease
2. Surgery
a. Only in pts where the focus is in one distinct area of the brain and Rx is unsuccessful
3. Epileptic people help control their seizures by avoiding things that provoke them (sleep deprivation, alcohol, etc)
EPILEPTIC STATUS
1. Seizures are often self-limiting but in cases when one is quickly followed by another without a recovery period the
patient is said to be in ES
2. Possible causes include
a. Metabolic (hypoxia, hypotension, -glycemia, and academia) which cause brain damage
b. Systemic Complications include cardiac arrhythmias, PE, hyperthermia and rhabdomyolysis
58 Sleep
Introduction Sleep Phases
During a normal sleep period there are 4-6 cycles of NREM-REM each lasting ~90min
1. REM
a. Rapid Eye Movement sleep which increases in duration as the cycles progress throughout the night
b. Cortical activity does exist in REM sleep and resembles that of an awake state
2. NREM
a. Has 4 stages noted for an increasing depth of sleep with an increased stimulus to elicit arousal
b. Eventually becomes REM sleep
Establishes the phase of a
rhythm via an environmental
Regulated Sleep Sleep-Wake Cycle
signal, such as a light
INTERNAL CLOCK
1. The suprachiasmic nucleus (SCN) in the anterior hypothalamus serves as an internal clock (endogenous rhythm)
2. SCN receives input from retinal ganglion cells which entrains internal time based on day-light cycles
3. This endogenous rhythm of the SCN strongly influences pineal gland to release melatonin (the dark hormone)
INTRINSIC RHYTHM OF SLEEP-WAKE CYCLE
1. Entrained by SCN so that healthy ppl sleep around midnight and wake around 7am
2. Without environmental stimuli (light), the day cycle slides to about 25 hours (see lecture 50-circadian clock)
3. In addition to the normal physiological tendency to sleep at night, many ppl tend to crave late-afternoon naps
4. The Ascending Reticular Arousal System is found in brainstem, hypothalamus and basal forebrain
a. Regulates the excitability of the cortex and thalamus
b. this activity declines with onset of sleep with small periodic increases with onset of REM sleep
SLEEP PROMOTING AGENTS
Connections between immune and sleep systems are noted to have a strong drive to sleep seen with infectious diseases
Some substances produced by the immune system are associated with infection-induced sleep
1. Interleukin-1
a. IL-1 concentration increases in the CSF during NREM sleep
b. Moreover, intraventricular injection of IL-1 causes NREM sleep
2. Delta Sleep-Induced Peptide
a. This peptide has been isolated from sleeping mammals and causes NREM with intraventricular sleep
3. Melatonin
a. Hits a max extracellularly at 2am and dwindles very low by 7am
b. Proven useful in jet-lag treatment, insomnia
c. Interestingly, melatonin stimulates wakefulness in nocturnal animals
4. Muramyl Peptides from Bacterial cell walls
a. Also produces NREM with intraventricular injection
5. Adenosine
a. A sleep promoting agent stimulating adenosine A1-receptors which are found at high concentrations in the
basal forebrain which can induce NREM sleep
b. Caffeine is said to work as an A1-inhibitor which gives it the capacity to inhibit sleep
Sleep Abnormalities
DOCUMENTED ABNORMAL PEOPLE
1. who sleeps for 1.5hours/night
2. war veteran with shrapnel in his pons exhibits virtually no REM sleep
3. observed in clinic experienced over 3hours of REM sleep
4. stayed awake for 11 straight days without any Rx and had no permanent harmful effects
HARMFUL EFFECTS OF SLEEP DEPRIVATION
1. Animals deprived of sleep die within several days
2. Legal execution of humans in the 1850s which could last for almost 19 days
3. Evidence of sleep deprivation is still used as a form of torture
4. Humans deprived of NREM sleep are irritable with marked performance in mental and manual skills
SLEEP DEPRIVATION - CONSEQUENCES
1. fMRI Tests Sleep vs. Non-Sleep
a. done on normal subjects during a mental tasks were compared to a sleep deprived person and it showed the
activity in the healthy person was nearly absent in the sleep deprived person
b. Sleep deprived people gave fewer answers and more incorrect
2. REM Sleep Deprivation
a. show an increased rebound need for more REM but not as much as for NREM
3. Cognitive deficits
a. NREM deprivation is much more significant that REM deprivation
4. Clinically Depressed People
a. have unusually large amounts of REM sleep where controlled deprivation can help alleviate their
symptoms either with behavior changes or Rx
5. Night Shift Workers
a. Even people who are accustomed to their late shift feel tired between 2-5am and is related to accidents
b. Night shift drivers in the UK are 5X more likely to have an accident
6. Blind Subjects
a. As seen previously, blind ppl have sleep issues which may be treated with prescribing melatonin
Sleep Abnormalities
1. ARAS (ascending reticular arousal system) Control of Wakefullness
a. Consists of three prominent neuron systems which use ACh, NE and Serotonin as the NT
b. Cell bodies located in the brain stem and basal forebrain
c. Keep cortex at proper level of excitability
d. Lesions of the brainstem can induce sleep/coma
e. General anasthetics lower consciousness by reducing the activity of the brainstem as part of the ARAS
2. Rhythmic Firing create Slow Waves
a. NREM (slow wave, low freq and synchronized) cortical activity w/o sensory input
b. Stage-2 NREM sleep spindles and K-complexes caused by these synchronized synapses in the cortex
i. Spindles: from rhythmic firing of thalamocortical neurons due to sensory and ARAS input
c. Stage-4 NREM delta waves caused by inherent synchronous firing of cortical cells
i. Due to absence of sensory input as well as direct ARAS input
Sleep Disorders
1. Insomnia
a. Can be transient, lasting ~3 weeks or chronic insomnia
b. Chronic can be caused by age, pain, psychiatric disorders, drugs or alcohol
2. Day-Time Sleepyness
a. Narcolepsy
i. Frequent day-time sleeping attacks, where pt enters REM sleep w/in 10min
ii. This is assoc. w/cataplexy (sleep paralysis) and hypnagogic hallucinations (pre-sleep dreams)
iii. This condition is treated with anphetamines (close watch on administration)
b. Sleep Apnea
i. Deprives people of night sleeping leaving them sleepy in the daytime
ii. Obstructive mechanical obstruction (upper airway)
iii. Central dysfunction of respiratory centers in the pons
iv. Mixed combined obstructive and central
v. Hypnograms show no stage 3 or 4 of NREM, thus NO REM causing severe sleep deprivation
vi. Latency to Sleep shortened from the normal 15min to ~3min (narcolepsy is ~2min)
c. Fatal Familial Insomnia
i. Untreatable; atrophy of thalamic nuclei; also includes memory and attention loss
ii. Overactivation of the ANS (sweating, hyperthermia, tachycardia, etc)
iii. This is a Prion Disease (prions are infectious lethal proteins)
3. Parasomnias
a. Sleepwalking
i. Occur w/in 1-2hrs of falling asleep at Stage-4 NREM
b. Nightmares and Sleep Tremors
i. Awakening from REM sleep with vivid memory of frightening dream
ii. Sleep Tremors are partial arousals from NREM, assoc w/sleep walking
c. Sleep Paralysis
i. Partial or complete flaccid paralysis and areflexia at the start or end of sleep
ii. Awareness is preserved and usually lasts a few seconds (often seen in narcoleptic pts)
4. Sleep Disorders and Abnormal Movement
a. Restless Leg Syndrome urge to move legs when sitting/lying down
i. Assoc w/ periodic limb movements every ~30sec during NREM, thus sleep
b. REM Behavior Disorder
i. Abnormal muscle movement during REM sleep assoc w/vivid dreams and are potentially harmful
59 Memory Systems
Forms of Memory
1. Declarative vs. Non-Declarative
a. Declarative conscious memory for facts, places and events
i. Involve hippocampal formation and diencephalon
b. Non-Declarative subconscious memory for skills, habits, emotional responses and some reflexes
i. Involve the striatum, cerebellum and amygdala; sometimes called procedural memory
2. Short vs. Long Term
a. New sensory information is processed into
intermediate memory for several seconds then into short term
b. This information, depending on the perceived importance,
may be consolidated into long term memory (days/yrs)
3. Amnesia
a. Retrograde loss of memory of past events before trauma
b. Anterograde inability to form new memories following trauma and remember only the past
4. Memory Traces Engram
a. An engram is a theory that states how memory is stored as a biophysical/biochemical change in the brain
b. Neural network or fragment of memory in a cluster of neurons connected together
Engrams
1. Location
a. Distributed in the neocortex grouped into association
areas which receive input from the primary visual,
auditory and somatosensory cortexes
b. The association areas then send new sensory info to
medial temporal lobes in the hippocampal formation
which then relays it right back to the association area
to consolidate into memory
c. Some areas are concerned with facts, events, places,
language and such while other are associated with
emotions, past events and people while others are for
working memory
2. Clinical Cases Reveal Engram Location
a. Removal of amygdala, uncus and most of hippocampus to treat epilepsy
i. Retained IQ, language, long term memory and ability learn new skills (procedural memory)
ii. Lost ability to make new memories (immediate/shortlong term impairment)
b. Lesion to thalamus, medial temporal lobe and mammillary body from fencing sword up the nose
i. Suffered anterograde amnesia
ii. Retained his IQ, language, procedural skill learning and 2yrs worth of long term memory
c. Stroke/TIA resulting in lesions to the hippocampus suffering marked loss of CA1 neurons
i. Suffered from anterograde amnesia and unable to form new declarative memories
ii. IQ, memories, & cognitive ability remained intact
a. Passage of information thru this loop induces synaptic plasticity at synapses on cells of the dentate gyrus,
hippocampus and subiculum
LONG TERM POTENTIATION - LTP
1. Hippocampus and Synaptic Plasticity
a. When CA1 is excited by CA3 impulse trains at high frequencies (100/s), the excitatory synapse
undergoes a long lasting increase in synaptic efficiency called long-term potentiation (LTP)
b. The potentiation takes place in glutamatergic synapses on dendritic spines in the CA1 neuron
2. LTP Caused by Postsynaptic Changes in CA1 Neurons
a. This long term potentiation is caused by an increase sensitivity to glutamate via insertion of new AMPA
receptors (review glutamate receptor AMPA/NMDA lecture 16)
b. Additionally, due to the formation of new dendritic spines between CA3 and CA1, the increased
number of synapses facilitates an increased responsiveness to synapses from CA3 to CA1
c. A single presynaptic impulse can open the AMPA receptors but the NMDAs remain blocked by the
resident Mg2+ ion however when a train of impulses arrive, it can open the NMDA channel and allows
Ca2+ ions to enter
d. These Ca2+ ions leads to activation of kinases which leads to AMPA receptors and eventual LTP
LTP SUMMARY
Increase in AMPA channel conduction (early)
Increase in the number of AMPA channels (early)
Increase in number of synapses via dendritic spine formation (late)
Remember that procedural/non-declarative memory is concerned with learned movements that can be recalled
Three major anatomical sites with functional synaptic connections to play a role:
o Supplemental & Premotor Cortex
o Striatum (in the basal ganglia)
o Cerebellum
LTD SUMMARY
A rise in intracellular calcium arising from the climbing fiber stimulation
A rise in intracellular sodium arising from the AMPA channel opening
An Activation of PKC from glutamate metabotropic receptor activation
Clinical Correlations
KORSAKOFFS SYNDROME
1. Occurring in chronic alcoholics with Thiamine deficiency
2. Atrophy of dorsomedial thalamus and mammillar bodies
3. Exhibit confusion, confabulation and severe memory impairment
a. Anterograde amnesia and severe retrograde amnesia prob due to damage to thalamus and hippocampus
4. May also exhibit lesions in neocortex, cerebellum and brainstem
ELECTROCONVULSIVE THERAPY
1. Employed to treat severe cases of clinical depression which electrically induces seizure
2. This is based on epileptics who are also depressed and showed marked improvement in depression following a
seizure
3. ECT may cause anterograde amnesia dating back several years but usually subsides a few months post-treatment
NEUROTOXINS FROM DINOFLAGELLATE PFIESTERIA PISCICIDA
1. This toxin released into the water can cause confusion, concentration, disorientation and severe memory loss
2. Contact may be inhaling or direct contact with the skin
Alzheimers Disease
AGING ASSOCIATED WITH ONSET
1. Causes of Dementia
a. Causes range from cerebrovascular disease, CNS infection, tumor, trauma, neurologic diseases like
Huntingtons and Parkinsons as well as MS
b. The most common form of Dementia is Alzheimers Disease whose cause/origin is uncertain
2. Alzheimers Disease
a. First described in 1907 and eventually classified into two types
i. Type-1: late onset after 65yrs
ii. Type-2: early onset before 65yrs
THREE CARDINAL SIGNS OF AD
1. Neuritic Senile Plaques
a. Extracellular spherical deposits containing many neuritic and glial processes with amyloid protein core
2. Neurofibrillary Tangles
a. Intracellular paired helical filaments
3. Granulovacuolar Degeneration
a. Degeneration caused by formation of intracellular circular clear zones of cytoplasm (vacuolation)
Clinical Correlations
1. Chromosome 21
a. Amyloid gene that encodes the A precursor Alzheimers Disease
b. Trisomy 21 gives rise to Downs Syndrome if they live past 40 will develop Alzheimers Disease
2. Prion Diseases
a. Is caused by an infectious protein known as a Prion
b. It is believed that the new variant of Creutzfeldt-Jakob disease was caused by eating contaminated beef
from a cow infected with a related animal prion disease known as bovine spongiform encephalopathy
3. Progeria
a. Rapid aging in children, evident by age 2 and death b/w 8-21 years of age from heart disease
b. Gene mutation causes defective protein that normally holds nucleus and cell together
Cranial Nerve Nuclei and many others (red nucleus, olive, raphe nuclei)
Tracts (ALS, Dorsal Column, Corticospinal, etc)
Reticular Formation
PPRF Lesion
1. Result of PPRF Lesion
a. Causes an ipsilateral conjugate horizontal gaze palsy, thus unable to look toward the affected side
b. The frontal eye field cannot communicate with the PPRF causing
i. Inability to aBduct the ipsilateral eye because no info is passed from the PPRF to abducens
ii. Since no info reaches the abducens, the contralateral occulomotor is not triggered thus the
contralateral eye is unable to aDDuct
2. Unopposed PPRF
a. The other PPRF is working fine however, so it is working unopposed and leads to a forced gaze toward the
unaffected side
Facial Palsy
1. Contralateral Central Facial lesion - UMN
a. Loss of lower facial muscles but still able to move forehead due to partial innervation from ipsilateral
cortex
2. Ipsilateral Central Facial Lesion - UMN
a. No loss because the majority of the innervation comes from the contralateral cortex
3. Peripheral Facial Lesion - LMN
a. Will result in total loss of muscle innervation on the ipsilateral side
Webers Syndrome
1. Cause
a. Lesion/infarction of the crus cerebri/cerebral peduncle in the midbrain
b. Usually due to infarction of the paramedian branches of the posterior cerebral arteries which supply
the area
2. Symptoms
a. Fibers passing thru or originating in this area which lost blood supply will manifest (see diagram)
3. Example of the Electrician (left infarction)
a. RIGHT SIDE (contralateral)
i. Arm/Leg weakness
ii. Facial weakness
iii. Hyperreflexia and rigidity in right arm
b. LEFT SIDE (ipsilateral)
i. Ptosis
ii. Medial Rectus paralysis
iii. CN-3 parasympathetic loss
Mid-Pontine Syndrome
1. Cause
a. Occlusion of short circumferential branches of the Basilar artery supplying the anterior pons
2. Symptoms (assuming Left-sided lesion)
a. RIGHT (contralateral)
i. Hemiplegia- weak extremities
b. LEFT (ipsilateral)
i. Face Trigeminal
1. Hemianasthesia
2. Paralyzed muscles of mastication
ii. Hemiataxia
1. Normal muscles but Ataxic
Wallenberg Syndrome
1. Cause
a. Stroke/infarc of brainstem caused by
occlusion to Vertebral artery or PICA
2. Symptoms
a. Aphagia
b. Hoarsness
c. Dizziness
d. N/V
e. Nystagmus
f. Improper gate and imbalance
g. No TP on one side of face
h. No TP on opposite side of body
i. Uncontrollable hiccups