(From Dr. Glasser’s Lecture, 18-21 July 2000, by Brian Buschman)
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The limbic lobe is a boarder between the diencephalon and the neocortex. It is a C-shaped structure starting as the subiculum and going to the cingulated, the isthmus and down to the parahippocampal gyrus. Associated with the parahippocampal gyrus is the entorhinal cortex (olfaction), hippocampus and dentate nucleus.
The limbic system is made up of the limbic lobe plus associated structures including:
1) Amygdaloid complex.
2) Septal nucli
3) Hypothalamus
4) Epithalamus
5) Parts of the thalamus
6) Nucleus acumbens of the striatum and ventral pallidum.
1) Fornix
2) Mamilothalamic tract
3) Stria terminalis
4) Stria medularis
5) Diagonal band
6) Medial forebrain bundle
1) Learning and memory
2) Emotional behavior (feeding behavior, how to play with others, sexual response).
The Papez circuit is the major circuit of the limbic system. It is the pathway of interconnection between limbic structures. If functions as a ring and can begin or end at any point in the ring. Starting at the entorhinal cortex we go:
1) The entorhinal cortex projects to the hippocampus.
2) The hippocampus sends the fornix to the mamillary bodies.
3) The mamillary bodies project to the anterior nucleus of the thalamus in the mamilothalamic tract.
4) The anterior nucleus of the thalamus will go to the cingulated gyrus in the anterior limb of the internal capsule.
5) The cingulated will go by the cingulum back to the entorhinal cortex.
The Papez circuit is associated with short term memory. We don’t know much about long term memory but know it must first go through short term.
Alcoholics will have a shortage of thiamine which will lead to damage of the mamillary bodies. Long term alcoholics will loose the ability to incorporate things to long term memory. This is why alcoholics will confabulate things to fill the gaps in what they don’t remember.
It has been shown that CA1 neurons in the hippocampus are destroyed by ACTH released by stress. CA1 neurons are important for incorporation of memory. Less stress will equal a better memory.
The hypothalamus is the primary ganglion of the ANS. The major limbic output is from the septal area (septum pellicudium) to the hypothalamus to the midbrain RF. The medial forebrain bundle (MFB) is the area that connects the septal area to the hypothalamus to the midbrain RF.
There are two limbic subsystems:
1) The hippocampal system which gets input from the parahippocampal gyrus (entorhinal cortex). The hippocampus has output to the mamillary bodies and onto the anterior nucleus of the thalamus. The hippocampus also feeds back to the septal area (see BRS Fig. 20-4).
2) The amygdaloid system gets input from the prefrontal, orbitofrontal and temporal cortexes. The amygdala sends outputs to the hypothalamus and the DM nucleus of the thalamus.
The hippocampus is found on the lateral boarder of the inferior horn of the lateral ventricle. The indusium griseum is a reminant of the hippocampus on the dorsal surface of the corpus callosum.
The hippocampus is made of three regions:
1) Dentate gyrus
2) Hippocampus proper (Made of the CA fields. CA for cornu ammonis.)
3) Subiculum
The center is the dentate gyrus. Then the hippocampus proper with CA1, CA2 and CA3 followed by the subiculum. The subiculum is the transition zone from the hippocampus (allocortex) to the parahippocampal gyrus (neocortex). The dentate gyrus is also allocortex. On the other end from the subiculum is the alveus which contains the hippocampal outflow tract and a few afferents.
The CA3 region will give fibers that enter the alveus to leave the hippocampus and o to the fornix. CA3 also sends projections called Schaffer collaterals to the CA1 area.
CA1 neuronal function is unclear but their loss causes major deficits of intellect and memory. CA1 neurons are the most sensitive neurons in the body when it comes to O2 deprivation. They are also destroyed by ACTH. Don’t stress too much or you will kill them and then you memory will stink.
There are four types of afferents to the hippocampus:
1) From the neocortex via the entorhinal cortex. The entorhinal cortex gets inputs from olfaction and from the cingulate gyrus (Papez circuit). Entorhinal cortical afferents also come from just about every different part of the cerebral cortex.
2) Septal area including nucleus basalis (substancia innominata). In Alzheimer’s patients there is a loss of nucleus basalis input (ACh) onto the CA1 neurons.
3) Contralateral hippocampus.
4) Structures from the RF such as locus cerillius (NE), raphe (5-HT), ventral tegmentum (dopamine). Some from the thalamus and hypothalamus.
Most of the hippocampal output is via the fornix. It goes from CA3 fibers and the subiculum to the alveus to the fornix. It goes from the fimbriae of the fornix to the crus, body and then into the column of the fornix.
The fornix is split by the anterior commisure into the:
1) Precommissural fornix going to the septal area.
2) Postcommissural fornix going to the mamillary bodies.
3) A small part going to nucleus acumbens and nucleus basalis.
The fornix does contain a few fibers that run in the opposite direction. The system then goes from the mamillary bodies to the anterior nucleus of the thalamus to the cingulate gyrus to the entorhinal cortex and back to the hippocampus in the Papez circuit. Some projections go from the mamillary bodies out in the mamilotegmental fasciculus back to the raphe, cerellius and tegmentum.
If you have a problem with the hippocampus and associated areas you will loose the consolidation of new memories. If you loose the dominant side hippocampus you loose memory associated with speech. If you loose the non-dominant hippocampus you loose new memories associated with everything else. Don’t worry you will still have all old, already incorporated, memories.
Declarative memory is memory for events and facts. What we have been talking about regarding the hippocampus is the process for incorporation of declarative memory. The process of forming procedural memories is completely different.
In chronic alcoholism there is often an intact intellect with an anterograde amnesia. The patient will commonly make up the story to fill the holes in what they actually remember. Autopsy shows thiamine induced hemorrhagic legions of the mamillary bodies.
Degradation of nucleus basalis and loss of ACh cause degenerative changes in the hippocampus of the entorhinal cortex that appear even before symptoms develop.
There is lots of 5-HT activity in sleep and it is thought that memories are incorporated when we are asleep. When asleep EEG shows that the hippocampus functions the way the rest of the brain does when awake. When awake the hippocampus functions as the rest of the brain does when asleep.
The amydgala functions in drive related behaviors and interacts with the septal nucli, hippocampus and prefrontal cortex. The amygdala interacts with many higher centers to ordinate emotional behavior. Only the ventrolateral amygdala is limbic as you should recall the corticomedial amygdala is primary olfactory cortex. It should be easy to see the tight tie in.
1) Septal nucli
2) Frontal lobe
3) Temporal lobe
4) Insular lobe
5) Cingulate gyrus
6) Thalamus
7) Hypothalamus
8) RF (Locus cerellius-NE, nuc. basalis-ACh, rahpe-5-HT, tegmentum-dopamine)
Projections via the amydgala to the stria terminalis will go to the:
1) Septal nucli
2) Hypothalamus
3) Contralateral amygdala via the anterior commisure
Septal nucli on the stria medularis to the habenular nucli will go to the interpeduncular nucli via the habenulointerpeduncular tract. Then it will go down to the RF and brainstem nucli. The septal nucli also projects down stream via the MFB.
The amygdala goes to the nucleus accumbens and to the MD nucleus of the thalamus to the prefrontal and orbital frontal cortexes.
The septal region is called the reward region because if you stimulate it a person reports feeling well and a feeling of warmth. If you stimulate the periaqueductal gray they will feel unbearable pain. Stimulation of the amygdala will produce fear, aggression and rage.
It is believed the role of the amygdala is to create subjective feeling with interactions with the hypothalamus and such. If you destroy the amygdala you are unable to remember the proper emotional response to a given stimuli.
The hippocampus will help you learn an event. The amygdala will help you learn if it is good or bad.
The amygdala uses autonomic responses to help establish a connection between sensory input and an effected state.
The syndrome is associated with a temporal lobe legion and causes:
1) Fearlessness
2) Lack of emotion
3) Hypersexuality (loss of pyriform cortex)
4) Hyperorality (wants to sense all objects orally)
We have two types of memory:
1) Declarative for facts and events. It’s incorporation is associated with the hippocampus and temporal lobe.
2) Procedural which functions through the striatum and cerebellum.
To consolidate short term working memory into long term declarative requires an intact hippocampus. Alzheimer’s ultimately causes destruction of CA2 nurons and thereby destroys memory.
Wernicke’s psychosis is from damage to the mamillary bodies. The amygdala is important with emotions and probably works with the hippocampus to encode emotional memories.
Memories are stored all over the neocortex in different places near the association areas for the given type of memory. Temporal lobe stimulation can cause a change in perception of the surroundings. Patients may feel strange in familiar places or feel at home in places they have never seen before.
Working memory is temporarily stored in regions of the prefrontal cortex. It is then relayed to the perihippocampal and entorhinal cortexes and on to the hippocampus. Hippocampal output via CA3, alveus and through the fornix. To form a memory there is some mechanism by which the system must strengthen some type of neural circuits.
There must be communication between the two hippocampal hemispheres if memories are to include both verbal and non-verbal associations.
We are not really sure but it must be either related to making new connections or strengthening existing ones. The formation of memories is almost immediate. If you try to block it an hour or two later it’s already in there.
We know that there are NMDA receptors that are associated with the process. They are stimulated by Glu and cause long-term potentiation (LTP) which allows CA2+ to enter the cells for a long time period.
A progressive loss of short term memory followed by a cognitive loss of general function. Alzheimer’s accounts for about 50-60% of cases of senile dementia. It has to do with decreases of ACh fro the nucleus basalis, epically onto CA1 neurons.
Early changes in Alzheimer’s include atrophy of the hippocampus and entorhinal cortex with can be seen on an MRI up to two years before the onset of clinical symptoms. The definitive diagnosis can only happen on autopsy based on finding:
1) Intracellular neurofibrillary tangles.
2) Extracellular plaques that are made up of extra fibers that are twisted into bundles.
3) Glia cells that surround a core of b-amyloid.
To have consciousness it’s required that a patient have the reticular activating system and at least one functioning cortical area. That type of life would stink but you need at least that to be consciousness.
Collectively the prefrontal and orbital frontal cortexes make up all of the frontal cortex other then areas 4, 6 and 8.
Phineas Gauge was the railroad worker that lost his prefrontal and orbital frontal areas with the spike accident. He and other patients that loose the prefrontal/orbital frontal cortexes:
1) Poor concentration span.
2) Ignores social norms.
3) Not aggressive.
4) Loss of abstract reasoning.
The prefrontal cortex gets inputs from all sensory association areas and is where working memory is believed to be stored. Patients with damage to the prefrontal cortex show the above symptoms.
The orbital frontal cortex gets massive limbic system input. Orbital frontal damage is associated with:
1) Compulsive behavior
2) Trouble repressing inappropriate actions.
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