Limbic system

The limbic system (or Paleomammalian brain) is a set of brain structures including the
hippocampus, amygdala, anterior thalamic nuclei, and limbic cortex, which support a
variety of functions including emotion, behavior, long term memory, and olfaction.[1]
The term "limbic" comes from Latin limbus, loosely translating as "border" or "belt".

Structures:
• Amygdala

• Χινγυλατε Γψρυσ

• Φορνιξ

• Ηιπποχαµπυσ

• Ηψποτηαλαµυσ

• Ολφαχτορψ Χορτεξ

• Τηαλαµυσ

Anatomy
Essentially the limbic system is the set of brain structures that forms the inner border of
the cortex. In an abstract topological sense, each cortical hemisphere can be thought of as
a sphere of gray matter, with a hole punched through it in the area where nerve fibers
connect it to the subcortical structures of the basal forebrain. The hole is surrounded by a
ring of cortical and noncortical areas that combine to make up the limbic system. The
cortical components generally have fewer layers than the classical 6-layered neocortex,
and are often classified as allocortex or archicortex.
The limbic system includes many structures in the cerebral cortex and sub-cortex of the
brain. The term has been used within psychiatry and neurology, although its exact role
and definition has been revised considerably since the term was introduced.[2] The
following structures are, or have been considered to be, part of the limbic system:
Amygdala: Involved in signaling the cortex of motivationally significant stimuli such as
those related to reward and fear in addition to social functions such as mating.
Hippocampus: Required for the formation of long-term memories and implicated in
maintenance of cognitive maps for navigation.
Parahippocampal gyrus: Plays a role in the formation of spatial memory Cingulate gyrus:
Autonomic functions regulating heart rate, blood pressure and cognitive and attentional
processing Fornix carries signals from the hippocampus to the mammillary bodies and
septal nuclei.
Hypothalamus: Regulates the autonomic nervous system via hormone production and
release. Affects and regulates blood pressure, heart rate, hunger, thirst, sexual arousal,
and the sleep/wake cycle
Thalamus: The "relay station" to the cerebral cortex

Function:

• Controls Emotions

• Emotional Responses

• Hormonal Secretions

• Mood

• Motivation ,Pain and Pleasure Sensations

The limbic system operates by influencing the endocrine system and the autonomic
nervous system. It is highly interconnected with the nucleus accumbens, the brain's
pleasure center, which plays a role in sexual arousal and the "high" derived from certain
recreational drugs. These responses are heavily modulated by dopaminergic projections
from the limbic system. In 1954, Olds and Milner found that rats with metal electrodes
implanted into their nucleus accumbens repeatedly pressed a lever activating this region,
and did so in preference to eating and drinking, eventually dying of exhaustion.
The limbic system is also tightly connected to the prefrontal cortex. Some scientists
contend that this connection is related to the pleasure obtained from solving problems. To
cure severe emotional disorders, this connection was sometimes surgically severed, a
procedure of psychosurgery, called a prefrontal lobotomy (this is actually a misnomer).
Patients who underwent this procedure often became passive and lacked all motivation.
Evolution:
The limbic system is embryologically older than other parts of the brain. It developed to
manage 'fight' or 'flight' chemicals and is an evolutionary necessity for reptiles as well as
humans.
Recent studies of the limbic system of tetrapods have challenged some long-held tenets
of forebrain evolution. The common ancestors of reptiles and mammals had a well-
developed limbic system in which the basic subdivisions and connections of the
amygdalar nuclei were established.

The Limbic System

The limbic system is a complex set of structures that lies on both sides and underneath
the thalamus, just under the cerebrum. It includes the hypothalamus, the hippocampus,
the amygdala, and several other nearby areas. It appears to be primarily responsible for
our emotional life, and has a lot to do with the formation of memories. In this drawing,
you are looking at the brain cut in half, but with the brain stem intact. The part of the
limbic system shown is that which is along the left side of the thalamus (hippocampus
and amygdala) and just under the front of the thalamus (hypothalamus):

Hypothalamus
The hypothalamus is a small part of the brain located just below the thalamus on both
sides of the third ventricle. (The ventricles are areas within the cerebrum that are filled
with cerebrospinal fluid, and connect to the fluid in the spine.) It sits just inside the two
tracts of the optic nerve, and just above (and intimately connected with) the pituitary
gland.
The hypothalamus is one of the busiest parts of the brain, and is mainly concerned with
homeostasis. Homeostasis is the process of returning something to some “set point.” It
works like a thermostat: When your room gets too cold, the thermostat conveys that
information to the furnace and turns it on. As your room warms up and the temperature
gets beyond a certain point, it sends a signal that tells the furnace to turn off.
The hypothalamus is responsible for regulating your hunger, thirst, response to pain,
levels of pleasure, sexual satisfaction, anger and aggressive behavior, and more. It also
regulates the functioning of the parasympathetic and sympathetic nervous systems, which
in turn means it regulates things like pulse, blood pressure, breathing, and arousal in
response to emotional circumstances.
The hypothalamus receives inputs from a number of sources. From the vagus nerve, it
gets information about blood pressure and the distension of the gut (that is, how full your
stomach is). From the reticular formation in the brainstem, it gets information about skin
temperature. From the optic nerve, it gets information about light and darkness. From
unusual neurons lining the ventricles, it gets information about the contents of the
cerebrospinal fluid, including toxins that lead to vomiting. And from the other parts of the
limbic system and the olfactory (smell) nerves, it gets information that helps regulate
eating and sexuality. The hypothalamus also has some receptors of its own, that provide
information about ion balance and temperature of the blood.
In one of the more recent discoveries, it seems that there is a protein called leptin which
is released by fat cells when we overeat. The hypothalamus apparently senses the levels
of leptin in the bloodstream and responds by decreasing appetite. It would seem that
some people have a mutation in a gene which produces leptin, and their bodies can’t tell
the hypothalamus that they have had enough to eat. However, many overweight people
do not have this mutation, so there is still a lot of research to do!
The hypothalamus sends instructions to the rest of the body in two ways. The first is to
the autonomic nervous system. This allows the hypothalamus to have ultimate control
of things like blood pressure, heartrate, breathing, digestion, sweating, and all the
sympathetic and parasympathetic functions.
The other way the hypothalamus controls things is via the pituitary gland. It is neurally
and chemically connected to the pituitary, which in turn pumps hormones called releasing
factors into the bloodstream. As you know, the pituitary is the so-called “master gland,”
and these hormones are vitally important in regulating growth and metabolism.
Hippocampus
The hippocampus consists of two “horns” that curve back from the amygdala. It appears
to be very important in converting things that are “in your mind” at the moment (in short-
term memory) into things that you will remember for the long run (long-term memory). If
the hippocampus is damaged, a person cannot build new memories, and lives instead in a
strange world where everything they experience just fades away, even while older
memories from the time before the damage are untouched! This very unfortunate
situation is fairly accurately portrayed in the wonderful movie Memento.
Amygdala
The amygdalas are two almond-shaped masses of neurons on either side of the thalamus
at the lower end of the hippocampus. When it is stimulated electrically, animals respond
with aggression. And if the amygdala is removed, animals get very tame and no longer
respond to things that would have caused rage before. But there is more to it than just
anger: When removed, animals also become indifferent to stimuli that would have
otherwise have caused fear and even sexual responses.
Related areas
Besides the hypothalamus, hippocampus, and amygdala, there are other areas in the
structures near to the limbic system that are intimately connected to it:
The cingulate gyrus is the part of the cerebrum that lies closest to the limbic system, just
above the corpus collosum. It provides a pathway from the thalamus to the hippocampus,
seems to be responsible for focusing attention on emotionally significant events, and for
associating memories to smells and to pain.
The septum, which lies in front of the thalamus, has areas that seem to be centers for
orgasm.
The ventral tegmental area of the brain stem (just below the thalamus) consists of
dopamine pathways that seem to be responsible for pleasure. People with damage here
tend to have difficulty getting pleasure in life, and often turn to alcohol, drugs, sweets,
and gambling.
The basal ganglia (including the caudate nucleus, the putamen, the globus pallidus, and
the substantia nigra) lie over and to the sides of the limbic system, and are tightly
connected with the cortex above them. They are responsible for repetitive behaviors,
reward experiences, and focusing attention. If you are interested in learning more, click
here.
The prefrontal cortex, which is the part of the frontal lobe which lies in front of the
motor area, is also closely linked to the limbic system. Besides apparently being involved
in thinking about the future, making plans, and taking action, it also appears to be
involved in the same dopamine pathways as the ventral tegmental area, and plays a part
in pleasure and addiction.

MEDIAL TEMPORAL LOBE (THE LIMBIC SYSTEM)
On the medial surface of the temporal lobe are three structures 
critical for normal human functioning. From rostral to caudal, they 
are the olfactory cortex, the amygdala, and the hippocampus. We 
will look at the anatomy and function of each separately, although 
they are often grouped together as "the limbic system".

A. The olfactory system:
The olfactory system actually begins in the roof of the nasal cavity. 
The olfactory receptors are ciliated epithelial cells with an array of 
receptors capable of detecting thousands of different odors. 

However, just as with any sensory system, the receptor neurons 
themselves do not project to the cerebral hemispheres. Their axons 
project up through the cribiform plate of the skull to synapse on the 
dendrites of the mitral cells of the olfactory bulb. The axons of the 
olfactory receptors make up the elusive cranial nerve I. This fragile 
tract is susceptible to shearing forces in head trauma, and loss of 
smell is a surprisingly debilitating injury.
Here is an example of a section 
through olfactory bulb. The 
olfactory bulb is not a simple 
relay (something which 
passively transmits the signal), 
but is a sophisticated structure 
in itself. The mitral cell­ 
olfactory neuron synapse is 
actually within a tangle of 
axons and dendrites that is 
called a glomerulus. There is a 
second cell type tucked 
around these glomeruli which 
probably affects how the 
signal is transmitted. These 
cells are small and densely 
packed, which gives them the 
name "granule cells". 
However, they bear no relation 
to the granule cells of the 
cerebellum or cerebral cortex. 
In fact, they are GABA­ergic, 
unlike other cells of the same 
name.

There are two populations of 
granule cells in the olfactory 
bulb ­ the external, or 
periglomerular cells, and the 
internal granule cells. The 
latter lie deep to the mitral cell 
 layer.

The mitral cell axons travel back to the brain via the olfactory tract. 
The main target of the olfactory tract is the primary olfactory cortex 
in the medial temporal lobe. However, the sense of smell is heavily 
interconnected with all parts of the limbic system. 

Does anything about this system strike you as odd? The olfactory 
system disobeys a general rule of sensory systems ­ it does not have to 
pass through thalamus before reaching cortex. However, there is a 
very good reason why not; olfactory cortex is an old and primitive 
structure, and in fact has only four cellular layers, unlike the 6­layered 
cortex we are accustomed to. The rule that sensory information must 
pass through thalamus to get to cerebral cortex is still true, but only 
for 6­layered cortex, or neocortex. This description applies to almost 
every area in the frontal, parietal, occipital, and temporal lobes. 

B. The amygdala:

If you remember only one word about the amygdala, the word is 
FEAR. The amygdala is the nucleus responsible for the lurch you feel 
in your stomach when you turn around in a dark alley and notice 
someone following you. It couples a learned sensory stimulus (man 
in ski mask in alley = danger) to an adaptive response (fight or flight). 
On the basis of this information, you should be able to guess the 
primary inputs to and outputs from the amygdala.

Inputs: the amygdala must get sensory input, and it must be fairly 
highly processed input to recognize the elements of a scene that 
signal danger. The association areas of visual, auditory, and 
somatosensory cortices are the main inputs to the amygdala.

Outputs: the amygdala must be able to control the autonomic system, 
to provoke such an instant sympathetic response. The main outputs 
of the amygdala are to the hypothalamus and brainstem autonomic 
centers, including the vagal nuclei and the sympathetic neurons. 

The amygdala is also involved with mood and the conscious 
emotional response to an event, whether positive or negative. To this 
end, the amygdala is also extensively interconnected with frontal 
cortex, mediodorsal thalamus, and the medial striatum.

These two images of the amygdala demonstrate that there are discrete 
groups of cells within the large nucleus. The deep group, which 
includes the lateral, basal, and accessory basal nuclei, is responsible 
for collecting the input from sensory cortex. The more dorsal group, 
which includes the central and medial nuclei, receives projections 
from the deep group and sends the signal out to autonomic centers. 

It is very difficult to study the amygdala in humans, because selective 
bilateral damage of the amygdala is so rare. One of the few existing 
case studies reported a woman with a bilateral degenerative disease 
who was unable to recognize the expression of fear in human faces. 
Monkeys with lesioned amygdalas are unable to recognize the 
emotional significance of objects, and for example, show no fear 
when presented with a snake or another aggressive monkey. This has 
disastrous social consequences for the monkey. 

Epilepsy surgery provides an opportunity to stimulate areas of the 
brain to determine the extent of the epileptic focus. In some such 
patients, the amygdala was electrically stimulated, which caused 
intense hallucinations, often accompanied by fear. 

C. The hippocampus and memory:

If the amygdala is FEAR, then the hippocampus is MEMORY. To 
understand exactly how the hippocampus is involved in memory, 
however, you must first know a little about memory.

There are at least three different types of memory. The most short 
term is working memory. Working memory is like the RAM of a 
computer. It is the type of memory that enables you to spit back the 
last sentence of a coversation when someone accuses you of not 
listening. Like the RAM of a computer, it is crucial for performing 
some common operations in your head: adding numbers, composing 
a sentence, following directions, etc. Also like a computer, the space 
devoted to that operation is recycled as soon as you turn to something 
else. It does not become a permanent memory. Working memory 
does not require the hippocampus; it is probably a cortical 
phenomenon.

The second type is what we most commonly associate with 
"memory". This is long­term or declarative memory, and is 
composed of all the facts, figures, and names you have ever learned. 
All of your experiences and conscious memory fall into this category. 
It is analogous to the hard drive of a computer. Although no one 
knows exactly where this enormous database is stored, it is clear that 
the hippocampus is necessary to file away new memories as they 
occur.

The third type is procedural memory, and is probably the most 
durable form of memory. These are actions, habits, or skills that are 
learned simply by repetition. Examples include playing tennis, 
playing an instrument, solving a puzzle, etc. The hippocampus is not 
involved in procedural memory, but it is likely that the cerebellum 
plays a role in some instances. 

The significance of the hippocampus is driven home by a famous 
patient named H.M. As part of an epilepsy surgery, doctors removed 
most of his medial temporal lobes. Since that surgery, in 1953, he has 
formed no new memories. He can remember his childhood and 
everything before the surgery, and he still has working memory and 
the ability to form procedural memories. You can have a normal, 
lucid conversation with him, but if you leave the room for a moment, 
when you return he will not remember you or the conversation. He 
has completely lost the ability to lay down declarative memory.

Therefore, the hippocampus is critical in laying down declarative 
memory, but is not necessary for working memory, procedural 
memory, or memory storage. Damage to the hippocampus will only 
affect the formation of new declarative memories.

The mechanisms of the hippocampus are not entirely understood. 
The formation of memories probably involves long term 
potentiation, or LTP. This is a molecular process which strengthens 
groups of synapses that are repeatedly used. LTP is not sufficient to 
explain the storage of memory, though. 

D. The anatomy of the hippocampus:

The hippocampus is a scrolled structure located in the medial 
temporal lobe. In a coronal section, it looks like this:
The hippocampus can be divided into at least five different areas, as 
labeled above. The dentate gyrus is the dense dark layer of cells at the 
"tip" of the hippocampus. Areas CA3 and CA1 are more diffuse; the 
small CA2 is hard to distinguish between them. (CA stands for cornu  
ammonis, from its ram's horn shape.) The subiculum sits at the base 
of the hippocampus, and is continuous with entorhinal cortex, which 
is part of the parahippocampal gyrus. There is essentially a one­way 
flow of information through the hippocampus, as diagrammed 
below.

Information enters the hippocampus by jumping across what appears 
to be a gap between the subiculum and dentate gyrus. This tract is 
called the perforant path, as it perforates the space between the two. 
The entorhinal axons then synapse on cells in the dentate gyrus. The 
dentate neurons, in turn, send axons to CA3; these are called mossy 
fibers. ("Mossy fibers" is a morphological description for axons with 
large bulbous terminals, and these are unrelated to those in the 
cerebellum.) CA3 sends axons called Schaeffer collaterals to CA1, 
which sends yet another set of fibers to the subiculum. The 
subiculum is responsible for the output of the hippocampus: it can 
either send axons directly to the hypothalamus and mammillary 
bodies via the fornix (remember the fornix?), or it can pass along the 
information back to entorhinal cortex, which will relay it all back to 
sensory cortex. It is essentially one continuous pathway that begins in 
sensory cortex, traverses the hippocampus (loop­the­loop), and 
returns to sensory cortex. Somewhere in there, memory is born.

E. Diseases of the hippocampus:

The hippocampus is particularly vulnerable to several disease 
processes, including ischemia, which is any obstruction of blood flow 
or oxygen deprivation, Alzheimer's disease, and epilepsy. These 
diseases selectively attack CA1, which effectively cuts through the 
hippocampal circuit. Below is a photograph of a normal 
hippocampus and one which has been deprived of oxygen.

You should be able to see the degeneration of CA1 (labeled) and the 
absence of cell bodies (stained purple). A stroke can have this effect, 
but there must be bilateral damage of the hippocampi to affect 
memory. Therefore only situations that deplete blood or oxygen flow 
to the entire brain will produce a memory deficit. The pathology of 
severe temporal lobe epilepsy looks very similar to ischemic damage.

Alzheimer's disease, although it affects the entire brain, is particularly 
hard on the CA1 region. Below is a photograph of the hippocampus 
of an Alzheimer's patient, with the CA1 region magnified. Both 
extracellular plaques and intracellular tangles are visible ­ these are 
the pathological hallmarks of the disease.