Limbic System

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

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Χινγυλατε Γψρυσ

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Φορνιξ

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Ηιπποχαµπυσ

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Ηψποτηαλαµυσ

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Ολφαχτορψ Χορτεξ

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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

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Emotional Responses

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Hormonal Secretions

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Mood

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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 welldeveloped 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 shortterm 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.