15. Olfaction and the limbic system

Question 1

Describe the parts of the olfactory epithelium.

Answer 1

• Bipolar Olfactory Neurones - these have two processes - projecting from base of the skull to the cribriform platw
• 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 and in degenerative diseases such as parkinsons and alzheimers

Question 2

Explain the organisation of the olfactory system

Answer 2

• 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 cortex in the temporal lobe 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

Question 3

Define anosmia.

Answer 3

• 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

Question 4

Answer 4

• 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

Question 5

Define the limbic system.

Answer 5

• 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

Question 6

What is the function of the limbic system?

Answer 6

• 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

Question 7

Describe the structure of the amygdala.

Answer 7

• 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

Question 8

Describe the Papez circuit.

Answer 8

• Papez Circuit = a neural circuit for the control of emotional expression
• 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 to the hypothalamus (mammillary bodies)
• 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
• NOTE: 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)

Question 9

What does diffusion tensor imaging do?

Answer 9

• 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

Question 10

Describe the afferent and efferent pathways of the Hippocampus.

Answer 10

• Afferent: 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
• Efferent: Fimbria/Fornix
  
  • This is the output pathway from the hippocampus
  • This is part of the Papez circuit

Question 11

What is the function of the hippocampus? What can happen to it when diseased?

Answer 11

• Functions:
  
  • Memory + Learning
• Clinical:
  
  • Alzheimer’s Disease
  • Epilepsy
• The hippocampus is in the medial temporal lobe
• In Alzheimer’s disease you get quite severe shrinking of the hippocampus – short time memory loss
• If you suspect that the patient is developing Alzheimer’s disease, you may see progressive shrinking of this area
• Hippocampus sits in the ventricle in the image of the medial temporal lobe

Question 12

Describe the structures of the limbic system from the top down

Answer 12

• 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

Question 13

Describe the image.

Answer 13

• 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

Question 15

Describe the coronal section of the hippocampus.

Answer 15

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 pathways

MAIN POINT: the hippocampus and entorhinal cortex are close together and are connected via the perforant pathway

Question 16

What happens to the brain during alzheimers? (atrophy)

Answer 16

• 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
• Hippocampus shrinks
• There has also been a widening of the sulci
• Frontotemporal tends to be damaged more so than the occipital in Alzheimer’s disease
• An atrophic hippocampus is a good clue for Alzheimer’s disease
• Occipital and frontal lobe are largely unaffected

Question 17

When do tau proteins show up in microscopy?

Answer 17

• 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 à it is hyperphosphorylated

Question 18

Describe Senile Plaques

Answer 18

• This is extracellular pathology
• You get lumps of protein sitting in between the cells in the neuropil

Question 19

Describe the anatomical progression of alzheimers disease.

Answer 19

• Early
  
  • Hippocampus and Entorhinal Cortex
  • Leads to short-term memory problems
• Moderate
  
  • 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 (inability to conduct normal activities such as riding a bike)
• Late
  
  • Frontal Lobe
  • Loss of executive skills + personality + interactions
• In general, Alzheimer’s disease will progress through the brain in this order with this pattern of symptoms arising

Question 20

Explain the afferent and efferent pathways of the amygdala.

Answer 20

• Afferent:
  
  • Olfactory Cortex
  • Septum (at the base of the septal membrane you have septal nuclei)
  • Temporal neocortex
  • Hippocampus
  • Brainstem
• Efferent:
  
  • Stria Terminalis – goes to the hypothalamus but further back

Question 21

Where is the amygdala located?

Answer 21

• This is buried in the white matter of the anterior temporal lobe and it has connections to basically everything

Question 22

What is the function of the amydala? What happens to it in degenerative diseases=

Answer 22

• Function: Fear and Anxiety + Fight or Flight
• It tends to be the focus of degenerative disease
  
  • In Alzheimer’s and Parkinson’s Disease the amygdala starts showing pathology early on
  • This can go in two directions: you can have people who are terrified of everything or you can get people who are totally disinhibited and can become quite aggressive
    
    • Management: sedatives

Question 23

Describe Kluver-Bucy syndrome.

Answer 23

• Syndrome resulting from bilateral lesions of the anterior temporal lobe (including amygdaloid nucleus)
• The syndrome was originally described in monkeys with bilateral temporal lobectomy
• Symptoms:
  
  • Hyperorality
    
    • 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
  • Hypersexuality

This is another basic instinct that becomes particularly prominent

Question 24

What structures are shown to be associated with aggression?

Answer 24

• Hypothalamus
• Brainstem (periaqueductal grey matter)
• Amygdala
• Serotonin (aka 5-HT) in the raphe nuclei of the brainstem appear to also be involved in aggression

Question 25

Describe the afferent and efferent connections of the septum.

Answer 25

Septum – membrane that divided 2 lateral ventricles

• Main Connections:
  
  • Afferent:
    
    • Amygdala
    • Olfactory Tract
    • Hippocampus
    • Brainstem
  • Efferent:
    
    • Stria medularis thalami
    • Hippocampus
    • Hypothalamus

Question 26

Explain the role of dopamine in the limbic system. How do opioids work?

Answer 26

• 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:
  
  • Cortex
  • Amygdala
  • 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
• L-DOPA is given to Parkinson’s patients – this increases levels of dopamine being released à next line of treatment: dopamine receptor agonists (you have to make family aware of side effects – obsessive compulsive activity such as gambling)
• Other neurotransmitters also modify this system