Olfaction and the limbic system

Question 1

What is important to remember about the limbic system

Answer 1

Defintions are quite nebular and will vary between different textbooks.

Question 2

What is important to remember about the olfactory system

Answer 2

Not very well defined in humans- the olfactory bulb is tiny- we do not preferentially use smell as a key sense- but in rodents- olfaction takes up a large part of their frontal cortex

Question 3

Where is the olfactory epithelium located

Answer 3

Olfactory receptors are located in the dorsal epithelial lining of the nasal cavity

Question 4

Summarise the anatomy of the olfactory system

Answer 4

§ We can smell between 2000-4000 different odours.
§ The molecular mechanisms are largely unknown.
§ Olfactory epithelium contains:
o Bipolar olfactory neurones.
o Sustentacular cells – sustaining cells.
o Basal cells – regenerative stem cells.
§ There is a progressive loss of olfactory epithelium with age.
§ The olfactory bulb projects neurones through fenestrations in the ethmoid bon

Question 5

What are the 3 types of cells that make up the olfactory epithelium

Answer 5

Bipolar Olfactory Neurones
Sustentacular Cells – support cells mainly providing metabolic support
Basal Cells – there is some regeneration in olfactory neurones

Question 6

Describe one potential molecular mechanism for the sense of smell

Answer 6

Odours (usually small, lipid-soluble, volatile molecules) enter the mucous film of the olfactory epithelium and diffuse to the receptor cell cilia. Interaction with specific binding proteins on the ciliary surface results in changes in a second-messenger pathway. Most odorant receptors are coupled to cyclic adenosine monophosphate (cAMP). On binding of an odorant molecule, the resultant rise in cAMP opens a cation channel causing depolarization that is proportionate to the concentration of the odorant.

Question 7

What is the function of the olfactory system

Answer 7

To process information about the idendity, concentration, and quality of a wide range of airborne, volatile chemical stimuli called odorants.

Question 8

What does each olfactory sensory neuron express

Answer 8

Each olfactory sensory neuron expresses only a single type of odorant receptor which binds a range of related molecules with varying affinities. There are many olfactory receptor proteins, which allow recognition of thousands of different odorants and at very low concentrations (parts per 10^12).

Question 9

Describe the importance of the basal cells

Answer 9

Allow the potential regeneration of olfactory sensory neurones

Question 10

What may progressive loss of smell be indicative of

Answer 10

Could be an early sign of neurodegenerative disease- such as Alzheimer’s or Parkinson’s

Question 11

Where do the olfactory sensory neurones then travel to

Answer 11

Axons arising from the receptor cells project through the cribiform plate ( a thin perforated region of the skull that separates the olfactory epithelium from the brain) directly to neurones in the olfactory bulb (which is found at the base of the frontal lobe)

Question 12

Describe the glomeruli in the frontal lobe

Answer 12

The fibres of the olfactory nerve (cranial nerve I) pass through the roof of the nose, which is formed by a perforated bone called the cribriform plate. They synapse in the olfactory bulb at the base of the frontal lobe in regions called ‘glomeruli’. Glomeruli are odour-specific functional units, each receiving approximately 25000 olfactory receptor neurons which respond to the same odours. Glomeruli are made up of the diffusely branching dendritic networks of mitral cells, tufted cells (output cells projecting to higher olfactory areas) and periglomerular cells (local inhibitory neurons)

Question 13

Which cells synapse within the olfactory bulb

Answer 13

The bipolar cells pass their axons through the cribriform plate to synapse with the second order neurones (olfactory bulb mitral cells) in the glomerulus within the olfactory bulb

Question 14

What structure do the second order neurones form and what does this structure split into?

Answer 14

Olfactory tract

It splits to form the medial and lateral olfactory stria

Question 15

Where does higher processing of smell take place?

Answer 15

Piriform cortex and orbitofrontal cortex

Question 16

Describe how olfactory processing begins in the bulb

Answer 16

The circuitry in the olfactory bulb allows higher olfactory areas to have an influence on output cell activity; also, output can be inhibited by the incoming olfactory information (Fig. 10.3). The complexity of this circuit allows olfactory processing to begin in the bulb. Lateral inhibition increases the contrast between glomeruli that respond to similar odorants. Connections from the brainstem modify the responsiveness of mitral and tufted cells with respect to the behavioural state (e.g. hungry versus sated).

Question 17

Describe the connections of the olfactory system to the brainstem

Answer 17

Connections to brainstem promote autonomic responses

For example, the cephalic phase is initiated when you smell food

Question 18

Describe the Bowman’s glands

Answer 18

Mucus is produced by secretory specialisations called Bowman’s glands that are distributed throughout the olfactory epithelium. When the mucus layer thickens, a during a cold, olfactory activity decreases significantly.
The mucus secreted by Bowman’s glands traps and neutralises some potentially harmful agents

Question 19

Describe the sustentacular cells

Answer 19

Contain enzymes (cytochrome P450 and others) that catabolise organic chemicals and other potentially damaging molecules. In addition, macrophages found throughout the nasal mucosa isolate and remove harmful material- as well as the remains of degenerating cells of the olfactory epithelium.

Question 20

Why is it important that the basal cells provide means for the olfactory receptor neurones to regenerate

Answer 20

ORNs have direct access to odorant molecules as air is inspired through the nose to the lungs; however, this access exposes these neurones to airborne pollutants, allergens, microrganisms, and other potentially harmful substances, subjecting more or less to continual damage.
The ultimate solution to the vulnerability of ORNs is to maintain a healthy population by a normal cycle of degeneration and regeneration, analogous to that in other exposed epithelia (gut and lung)
Maintain a population of neural stem cells (the basal cells)

Question 21

What is a clinical deficit in the olfactory system called?

Answer 21

Anosmia

Question 22

What is a common cause of anosmia

Answer 22

Damage to the cribriform plate (e.g. due to trauma) may section the olfactory nerve and result in anosmia. In addition, when inserting a nasogastric tube, it should be aimed straight towards the back of the head, and not upwards. Otherwise, the tube may pierce the cribriform plate and damage tissue posterior to it. It may be preferable to avoid nasogastric feeding.

Question 23

Describe the potential consequences of mid face trauma

Answer 23

Mid-face trauma
Impact with enough force could cause a fracture of the cribriform plate, shearing the neurones going from the olfactory epithelium to the olfactory bulb

Question 24

The piriform cortex is found within the medial temporal lobe. Explain the significance of this with regards to epileptic patients.

Answer 24

Epilepsy is often focused in the temporal lobe
This means that some people with epilepsy will experience PRODROMAL AURA (they are made aware of an imminent seizure because they’ll smell something that’s not there)

Question 25

Describe the link between Parkinson’s and anosmia

Answer 25

Parkinson’s-anosmia: ?environmental trigger - often early aspects include pathology of the olfactory bulb; initially present with loss of smell and diarrhoea

Question 26

Summarise olfactory pathways and pathologies

Answer 26

Olfactory bulb (mitral cells) à olfactory tract à olfactory stria (medial and lateral) à Piriform cortex (lateral stria), Orbitofrontal cortex (medial stria) à connections then promote autonomic responses.
§ A clinical deficit of smell is known as Anosmia.
§ In some epilepsy patients, prior to seizures they begin to smell something that isn’t there and this is known as Prodromal auras.
§ The olfactory bulbs are an early target for many pathologies, i.e. Parkinson’

Question 27

Describe the role of the piriform cortex

Answer 27

•

Pyriform cortex, which processes the discrimination between odours

Question 28

Where is the orbitofrontal cortex found

Answer 28

Frontal lobe- near the orbital bone.

Question 29

Ultimately, what is meant by the limbic system

Answer 29

Broca (1878) - rim or limbus of cortex adjacent to corpus callosum and diencephalon (on the medial face of the hemispheres)

Structurally and functionally interrelated areas considered as a single functional complex

Question 30

What is the limbic system a system of

Answer 30

The limbic system is a complex system of fibre tracts and grey matter. It was introduced above, lying in the medial aspect of each temporal lobe, encircling (limbus = border) the upper part of the brainstem. This serves as the ‘nervous system’ for emotion and behaviour. It also has extensive connections to both lower and higher parts of the central nervous system, allowing it to integrate a wide variety of stimuli.

Question 31

What are the key functions of the limbic system

Answer 31

System responsible for processes aimed at survival of the individual:
maintenance of homeostasis via activation of visceral effector mechanisms, modulation of pituitary hormone release and initiation of feeding and drinking- hypothalamus component
agonistic (defence & attack) behaviour
sexual & reproductive behaviour
memory (drives everything we do- we learn from our experiences)

Question 32

State two important parts of the limbic system that are found within the temporal lobes an what circuit are these structures apart of

Answer 32

Hippocampus and Amygdala

Papez circuit

Question 33

What is the limbic system composed of

Answer 33

Composed of – olfactory bulbs, hypothalamus, amygdala, hippocampus, thalamus and frontal lobe.

Question 34

Summarise the structure of the limbic system

Answer 34

Structures: mainly comprised of the amygdala anteriorly and the hippocampus posteriorly on the floor of the inferior horn of the lateral ventricle; cortical representation mainly consists of the cingulate cortex above the corpus callosum

Question 35

Summarise the papez circuit

Answer 35

The cingulate cortex and hypothalamus are interconnected by mammillary bodies (part of the posterior hypothalamus- two spheres at base of brain)
to the dorsal thalamus, which in turn projects to the cingulate gyrus.
The cingulate gyrus ( and many other cortical regions as well) projects to the hypothalamus. Finally, Papez showed that the hippocampus projects via the fornix ( large fibre bundle) back to the hypothalamus.
Papez suggested that these pathways provided the connections necessary for cortical expression.

Question 36

What is the function of the Papez circuit?

Answer 36

It is a neural circuit for the control of emotional expression

Question 37

Describe the pathway of the papez circuit

Answer 37

Hippocampus: present on the floor of the inferior horn of the lateral ventricle, outputting to the fornix
Fornix: fibre pathway from the inferior horn, passing under the corpus callosum to synapse in the mamillary bodies (hypothalamus)
Mammillo-thalamic tract: projects to the anterior nucleus of the thalamus
ANT: produces thalamo-cortical projections to the cingulate cortex
Cingulate cortex: allows for emotional colouring from the neocortex

Question 38

Describe the 3 core parts of the papez circuit

Answer 38

Hippocampus- emotional experience- lays down the new memory
Hypothalamus- emotional expression
Neocortex- emotional colouring

Question 39

What form of imaging is used to study the limbic system

Answer 39

Digital Tensor Imaging – shows co-instant activity in different parts of the brain thus showing which parts of the brain are working together
This imaging is used to theorise the pathways/networks in the brain to highlight parts of the brain that are interconnected when performing certain actions/functions (e.g. crying)

Used to image functional psychoses- such as schizophrenia- as these won’t show any brain pathology on autopsy- but they are functional connectivity issues

Question 40

Summarise the hippocampus

Answer 40

Main connections:
Afferent: Perforant pathway
Efferent: Fimbria/ fornix
Functions:
Memory & learning
Clinical:
Alzheimer’s disease, epilepsy

Question 41

Where can you find the hippocampus on a coronal MRI

Answer 41

The swiss roll structure

Question 42

Describe the afferent pathway of the hippocampus

Answer 42

Afferent Pathway = Perforant Pathway
The entorhinal cortex is linked to the hippocampus via the afferent pathway (perforant pathway)
The entorhinal cortex receives input from all other parts of the neocortex

Question 43

Describe the efferent pathway of the hippocampus

Answer 43

The efferent is known as the fimbria while the path is attached to the hippocampus, when it leaves, it becomes the fornix.

Question 44

Summarise the structure of the hippocampus

Answer 44

Hippocampus is the broad projections at the base of the triangle (on the floor of the lateral ventricles)
Main output is fornix which moves up and forward in the midline, lying immediately below the corpus callosum
Mammillary bodies lie at the end of the fornix
Isolated spheres are the amygdala (near the hippocampus) - not found in the ventricles- but in the white mater of the temporal lobe

Question 45

Describe the shape of the hippocampus

Answer 45

Sea-horse shaped

Dentate gyrus and major pyramidal cells joining the two sea-horses

Question 46

Describe the spatial relations of the hippocampus and the fornix to other important brain structures.

Answer 46

The hippocampus is found on the floor of the lateral ventricles
The fornix comes out of the hippocampus and passes under the corpus callosum
It then dives inferior and anteriorly towards the mammillary bodies

Question 47

Describe the appearance of advanced Alzheimer’s disease on a CT head scan in the coronal plane.

Answer 47

There will be extensive cortical atrophy
The ventricles would appear enlarged
There will also be widening of sulci

Question 48

Where does pathology associated with Alzheimer’s normally begin

Answer 48

In the transethorinal cortex - first appearance of tangles- appearance of Tau ( a microtubule associated protein- becomes disturbed.
Hippocampus is priamary in Alzheimer’s disease

Question 49

Describe the microscopic pathologies associated with Alzheimer’s

Answer 49

§ Tau immunostaining – in Alzheimer’s disease, sporadic tau proteins in the brain become hyper-phosphorylated and this stops them functioning so they die.
§ Senile plaques – alpha-beta proteins build up in the brain in Alzheimer’s and when there is too much, the cells excrete it and the proteins form toxic plaques.

Question 50

Describe tau immunostatining

Answer 50

Tau Immunostaining
· Intracellular pathology – the cytoskeleton has been compromised
· The tau proteins show up in the staining and allow the damaged neurones to be seen

Question 51

Describe senile plaques

Answer 51

Senile Plaques
· Extracellular pathology
· Lumps of protein sitting in between cells in the neuropil

Question 52

Describe the anatomical progression of Alzheimer’s disease, including the symptoms experienced

Answer 52

Early
· Hippocampus and entorhinal cortex affects
· Short-term memory problems
Moderate
· Parietal lobe (where you have your procedural memory) - damage leads to disorientation
· Example of effects: dressing apraxia (don’t know where fingers are)
Late
· Frontal lobe
· Loss of executive skills

Question 53

Summarise the amygdala

Answer 53

Main connections:
Afferent: Olfactory cortex ( a certain smell may provoke anxiety- for example gas), septum, temporal neocortex, hippocampus, brainstem
Efferent: Stria terminalis ( to anterior parts of the hypothalamus)
Functions:
Fear & anxiety (and opposite)
Fight or flight
Clinical:
Kluver-Bucy syndrome
Bilateral to temporal lobe anteriorly- trauma (hitting head on dash board in car crashes)- before air bags- temporal lobes smash against middle cranial fossa- causing damage- amygdala quite far forward- can get bilateral amygdala damage

Question 54

Describe Kluver-Bucy syndrome

Answer 54

o Kluver-Bucy Syndrome – post-trauma, temporal lobes are sheared off middle cranial fossa and amygdala damaged (including amygdaloid nucleus)
o Symptoms – hyperorality (putting things in mouth- revert to a baby like state), loss of fear, visual agnosia, hypersexuality.

Question 55

. In Alzheimer’s and Parkinson’s disease, the amygdala starts showing pathology early on. What are the possible outcomes of this?

Answer 55

Patients could either become terrified of everything or they could become totally disinhibited and become quite aggressive

Question 56

What is important to remember about the brain when looking at it in the coronal view

Answer 56

Note: cannot see horns of ventricles in coronal sections of the brain with the amygdala.

Question 57

Essentially, what is the amygdala

Answer 57

A grey mater nucleus embedded in the white mater of the anterior temporal lobe- in front of the ventricle
Multiple nuclei (corticomedial, central and basolateral) each of which appear to have differing sensitivities to neurodegeneration.

Question 58

Summarise Kluver-Bucy syndrome

Answer 58

Syndrome originally described in monkeys with bilateral temporal lobectomy
Hyperorality
Loss of fear
Visual agnosia
Hypersexuality

Question 59

Summarise aggression

Answer 59

Structures shown experimentally to be associated with aggression
Hypothalamus (anterior)
Brainstem (periaqueductal grey)- grey mater around aqueduct
Amygdala
5-HT in raphe nuclei- midline nuclei in brainstem

Question 60

What are the septal nuclei

Answer 60

The membrane lying between the lateral ventricles anteriorly

Question 61

Summarise the septal nuclei

Answer 61

Main connections:
Afferent: Amygdala, olfactory tract, hippocampus, brainstem
Efferent: Stria medularis thalami, hippocampus, hypothalamus
Functions:
Reinforcement & reward
(from the nucleus accumbens)

Question 62

Describe the potential therapeutic use of electrode stimulation to certain parts of the brain

Answer 62

Neurosurgeons can insert electrical devices that stimulate certain regions of the brain:
sub-thalamic nuclei- to control tremors in Parkinson’s
septal nuclei- to improve mood in clinically depressed individuals

Question 63

Describe the mesolimbic pathway

Answer 63

Mesolimbic pathway: DA pathway that originates in the ventral tegmental area of the midbrain, projecting via the medial forebrain bundle to the cortex, amygdala and nucleus accumbens

Question 64

What is important to remember about the mesolimbic pathway

Answer 64

The dopaminergic neurones are not the same as those that come from the substantia nigra and project to the striatum
Instead, they originate from the ventral tegmental area in the midbrain (just dorsal and medial to the substantia nigra)

Question 65

Summarise drug dependence

Answer 65

drugs of abuse e.g. Opioids and amphetamines increase dopamine release in the nucleus accumbens via:

Stimulating midbrain neurones
Promoting DA release
Inhibiting DA reuptake (cocaine)

Other NTs can also modify this system.

Question 66

What effect do all drugs of abuse have on the nucleus accumbens

Answer 66

They all increase dopamine release in the nucleus accumbens

Question 67

Why do you have to warn the family of patients when prescribing said patient a dopamine agonist

Answer 67

Due to the effects of dopamine of the nucleus accumbens- it can lead to obsessive compulsive behaviours and dopamine related side effects- in extreme examples patients have been known to develop gambling addictions and gamble their family home away.