Limbic system Flashcards
Olfactory anatomy: recognise the anatomical basis of the olfactory system
- 2000‐4000 different odours (little compared to other species like rats)
- The molecular mechanism is largely unknown
- Parts of the olfactory epithelium:
Bipolar Olfactory Neurones -‐ these have two processes
Sustentacular Cells -‐ support cells mainly providing metabolic support
Basal Cells -‐ unlike other parts of the brain, there is some regeneration of olfactory neurones throughout life
We progressively lose olfactory neurones as we age( early indication in Alzheimer’s or dementia)
Organisation of the Olfactory System
- The olfactory bulb is found sitting just above the cribriform plate
- In the upper part of the nose you find the olfactory epithelium
- The axons of the bipolar cells pass through the cribriform plate in the base of the skull up into the olfactory bulb
- These bipolar cells then synapse at a glomerulus with a second-‐order olfactory neurone which send their axons down the olfactory tract towards the brain
- The second-‐order olfactory neurones are called olfactory bulb mitral cells
- The olfactory tract splits to form two olfactory stria (medial and lateral)
- Higher processing of the smell goes on in the piriform and orbitofrontal cortices
- Damage to the piriform or orbitofrontal cortices can result in inhibition of normal smell processes
- There are some connections of the olfactory system to the brainstem because odours can promote autonomic responses e.g. salivating when you smell food
- Clinical Deficit in the Olfactory System: anosmia
- Common cause of anosmia = mid-‐face trauma
- If you get a smack of the nose that is serious enough to cause a fracture of the skull, you can break the cribriform plate and shear off the neurones going from the olfactory epithelium
Location of the olfactory system
Ventral view of the brain
You can see the olfactory tract splitting into a medial and lateral olfactory stria
The piriform cortex and orbitofrontal cortex is where most of the olfactory processing takes place
Epilepsy is often focused in the temporal lobe (and the piriform cortex is in the temporal lobe)
This means that some people with epilepsy will experience PRODROMAL AURA where they are made aware that they’re going to have a seizure because they’ll smell something that is not there
Neurodegenerative Disease and Anosmia
- Neurodegenerative disease is a relatively common cause of anosmia
- Pathology in the olfactory bulb is an early aspect of Parkinson’s and Alzheimer’s Disease
- Parkinson’s is a very sporadic disease with less than 5% of cases being due to autosomal dominant or recessive inheritance
- It is thought that there could be some sort of environmental trigger that will trigger Parkinson’s in susceptible individuals
- This stimulation may be through the gut (up the vagus nerve to the brainstem) or through the nose (there is little between the top of the nose and the brain)
- Presenting symptoms of Parkinson’s Disease patients may include loss of smell and diarrhoea
- This isn’t particularly useful because there are a lot of causes for these symptoms
Limbic system: explain the structure and function of the limbic system, and identify the functional effects of lesions to individual components of the limbic system
Limbic System
There are varying definitions
As described by Broca in 1878: the limbic system is a rim (or limbus) of cortex adjacent to the corpus callosum and diencephalon
The limbic system consists of structurally and functionally interrelated areas considered as a single functional complex
It is responsible for processes aimed at survival of the individual:
Maintenance of homeostasis via:
- Activation of visceral effector mechanisms
- Modulation of pituitary hormone release
- Initiation of feeding and drinking
- These are mainly HYPOTHALAMIC functions
Agonistic behaviour (defence & attack/fight & flight)
Sexual and reproductive behaviour
Memory
The basis of all emotional responses to the outside world is related to what you have experienced before
Structures of the Limbic System
The two parts that are key to the limbic system are found in the temporal lobe:
Amygdala (anteriorly)
Hippocampus (immediately behind the amygdala on the floor of the inferior horn of the lateral ventricle)
These two structures are part of the Papez Circuit
Within this circuitry there are several nuclei within the thalamus
Cortical representation of the limbic system: mainly the cingulate cortex which is just above the corpus callosum
Structures of the limbic system from the top down
- The sharp hollowed out area are the inferior horns of the lateral ventricles
- On the floor of the lateral ventricles you find the hippocampus on either side (the vaguely penis shaped things)
- The main output pathway of the hippocampus is the fornix which you can see moving up and forward in the midline and coming from the hippocampus on both sides
- The fornix lies immediately below the corpus callosum which has been cut out in this diagram
- The fibres of the fornix go forwards and will end up in the mammillary bodies at the base of the hypothalamus
Another view of the limbic system structures
- This shows an isolated view of the limbic system structures
- The hippocampus is the penis shaped thing at the bottom
- The fornix goes up and forwards and ends at the mammillary bodies
- The isolated grape shaped things near the hippocampus is the amygdala
- The amygdala is NOT in the ventricle, it is in the white matter at the front of the temporal lobe
Papez circuit: identify the components of the Papez circuit
Papez Circuit = a neural circuit for the control of emotional expression
This is a simple diagram showing how the different structures of the limbic system are linked together
- To start with, you have the hippocampus on the floor of the inferior horn of the lateral ventricle and its main output pathway is the fornix
- The fornix is the fibre pathway that comes out of the inferior horn, passes under the corpus callosum and dives down anteriorly to synapse in the mammillary bodies (in the hypothalamus)
- The mammillary bodies are particularly damaged in chronic alcoholism and Wernicke-‐Korsakoff Syndrome
- This is why these diseases involve amnestic issues
- From the mammillary bodies there is a fibre pathway called the mammillo-‐ thalamic tract (MTT), which projects to the anterior nucleus of the thalamus
- From the anterior nucleus of the thalamus there are thalamo-‐cortical projections, in this case, going to the cingulate cortex
- From the cingulate cortex, the loop is complete by fibres projecting back to the hippocampus via the cingulate bundle
- Your reaction to the outside world is ‘coloured’ by what you’ve experienced before and this emotional colouring is neocortical
- Other parts of the neocortex (e.g. frontal and parietal lobes) will all have input based on previous experience which affects how this circuit is working
- So this can be broadly broken down to emotional colouring, the emotional experience itself and emotional expression (your visceral/emotional response)
We have an input an interaction with the environment which will lay out a new memory – autonomic reaction – emotional expression is largely hypothalamic, everything you do is coloured by your previous experiences so thre is an emotional colouring aspects relating it to what has happened before
Coronal section of the hippocampus
You see the seahorse shape of the two interlocking Cs of the primary cells within the hippocampus -‐ this is why it is called hippocampus because that means ‘seahorse’
The key area next to the hippocampus is the entorhinal cortex which receives inputs from every other cortical area
The projections into the hippocampus from the entorhinal cortex is via the perforant pathway
The rest of the labels are just anatomical landmarks in the vicinity
MAIN POINT: the hippocampus and entorhinal cortex are close together and are connected via the perforant pathway
Cortical structures and imaging
Digital Tensor Imaging
This form of imaging shows co-‐instant activity in different parts of the brain
Hence it can show which parts of the brain are working together
A lot of understanding of the limbic system is based on this form of imaging
Brain of the schitzophrenic patient – functional connectivity issues but can’t see post portem, this type of imaging can give more info
Hippocampus
Main Connections:
- Perforant Pathway
The main connections are from the adjacent cortex (entorhinal cortex) through the perforant pathway and that adjacent piece of cortex receives input from every other neocortical area
Every other piece of the cortex sends some projections to the entorhinal cortex and from there via the perforant pathway you have input to the hippocampus
-
Fimbria/Fornix
- This is the output pathway from the hippocampus
- This is part of the Papez circuit
- Memory + Learning
- Alzheimer’s Disease
The hippocampus is in the medial temporal lobe
In Alzheimer’s disease, you get quite a severe shrinking of the hippocampus
Lesions
Cortical Atrophy
The atrophy progresses through the brain in a very stereotypical manner
Cortical atrophy is a general feature of Alzheimer’s though it is not unique to Alzheimer’s
There is a loss of neurones and the ventricles are much LARGER than they should be
In the top right image you see that the inferior horns of the lateral ventricle are much larger than they should be and the hippocampus has shrunk
There has also been a widening of the sulci
Frontotemporal tends to be damaged more so than the occipital in Alzheimer’s disease
Microscopic Hallmarks
Tau Immunostaining
This is intracellular pathology -‐ the cytoskeleton has become compromised
The dark structure is a damaged neurone that is going to die
It is the tau protein that shoes up in the staining and allows you to see the damaged neurones
Senile Plaques
This is extracellular pathology
You get lumps of protein sitting in between the cells in the neuropil
The Anatomical Progression of Alzheimer’s Disease
Hippocampus and Entorhinal Cortex
Leads to short-‐term memory problems
Parietal Lobe
This is where you have your procedural memory (doing the simple things
that you don’t normally thing about too much)
Dressing Apraxia
Frontal Lobe
Loss of executive skills
In general, Alzheimer’s disease will progress through the brain in this order with this pattern of symptoms arising
Emotion: summarise the brain systems involved in emotion, including fear, anxiety, anger, aggression, reinforcement and reward
Location of the Amygdala
Kluver-‐Bucy Syndrome
- Syndrome resulting from bilateral lesions of the anterior temporal lobe (including amygdaloid nucleus)
- The syndrome was originally described in monkeys with bilateral temporal lobectomy
- You start exploring things with your mouth again (like babies do)
Loss of Fear
Could be accompanied by aggression
Visual Agnosia
- Inability to recognise objects o Hypersexuality
- This is another basic instinct that becomes particularly prominent
Aggression
- Structures shown experimentally to be associated with aggression: o Hypothalamus
Brainstem (periaqueductal grey matter) o Amygdala (mainly fear)
Serotonin (aka 5-‐HT) in the raphe nuclei of the brainstem appear to also be involved in aggression
Limbic system: puts together anatomical
Septum
Main Connections: o Afferent:
Olfactory Tract
Stria medularis thalami
Don’t worry about the output pathway too much
Reinforcement and Reward
This is in the anterior part of the brain, quite far forward
The dark bits coming diagonally downwards (no. 17) are the internal capsules
Between the internal capsule and the lateral ventricle you have the caudate nucleus
The putamen is the thick yellow area that is lateral to the dark stain of the internal capsule
No. 16, the yellow shading that appears to be merging with the internal capsule is the nucleus accumbens (this is also involved in the reward system)
At the base of the septal membrane you get the septal nuclei (activated by good press in rodents)
Stimulation in these area as a treatment for terrors, if septal nuclei stimulated maybe useful
Drug dependence: define the dopaminergic pathway thought to mediate drug dependence
In Parkinson’s Disease, the motor problems arise from loss of dopaminergic cells in the substantia nigra in the midbrain projecting up to the basal ganglia
Breakdown of this circuitry underlies the tremulous presentation or the akinetic, rigid presentation
PD patients may want to move and have initiated the wish to move but because of the problem with the basal ganglia problem they can’t carry out the activity
There is a second dopaminergic pathway and this also comes from the midbrain but it comes from the VENTRAL TEGMENTAL AREA (VTA)
Projections from this dopaminergic nucleus goes via the medial forebrain bundle (MFB) to a number of different places:
Nucleus Accumbens -‐ important in drug dependence
VTN is more medial than the substantia nigra
The dopaminergic neurones of the substantia nigra project to the basal ganglia
The dopaminergic neurones of the ventral tegmental area project to the nucleus accumbens (among other places)
All drugs of abuse (opioids, nicotine, amphetamines, ethanol and cocaine)
ALL INCREASE DOPAMINE RELEASE IN THE NUCLEUS ACCUMBENS
They do this by different mechanisms:
Stimulate midbrain neurons
Promote DA release
Inhibit DA reuptake
E.g. cocaine inhibits DA reuptake thus
increasing the time that dopamine spends in the synapse
Other neurotransmitters also modify this system
Gambling 0 changing medication could resultin OCD which is a behaviour reinforcing gambling
Drug Independece
Opioids, nicotine, amphetamines, ethanol and cocaine all increase DA release in nucleus accumbens
Stimulate midbrain neurons, promote DA release or inhibit DA reuptake
Other neurotransmitters also modify this system
