Olfaction and the limbic system Flashcards
What is important to remember about the limbic system
Defintions are quite nebular and will vary between different textbooks.
What is important to remember about the olfactory system
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
Where is the olfactory epithelium located
Olfactory receptors are located in the dorsal epithelial lining of the nasal cavity
Summarise the anatomy of the olfactory system
§ 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
What are the 3 types of cells that make up the olfactory epithelium
Bipolar Olfactory Neurones
Sustentacular Cells – support cells mainly providing metabolic support
Basal Cells – there is some regeneration in olfactory neurones
Describe one potential molecular mechanism for the sense of smell
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.
What is the function of the olfactory system
To process information about the idendity, concentration, and quality of a wide range of airborne, volatile chemical stimuli called odorants.
What does each olfactory sensory neuron express
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).
Describe the importance of the basal cells
Allow the potential regeneration of olfactory sensory neurones
What may progressive loss of smell be indicative of
Could be an early sign of neurodegenerative disease- such as Alzheimer’s or Parkinson’s
Where do the olfactory sensory neurones then travel to
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)
Describe the glomeruli in the frontal lobe
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)
Which cells synapse within the olfactory bulb
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
What structure do the second order neurones form and what does this structure split into?
Olfactory tract
It splits to form the medial and lateral olfactory stria
Where does higher processing of smell take place?
Piriform cortex and orbitofrontal cortex
Describe how olfactory processing begins in the bulb
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).
Describe the connections of the olfactory system to the brainstem
Connections to brainstem promote autonomic responses
For example, the cephalic phase is initiated when you smell food
Describe the Bowman’s glands
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
Describe the sustentacular cells
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.
Why is it important that the basal cells provide means for the olfactory receptor neurones to regenerate
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)
What is a clinical deficit in the olfactory system called?
Anosmia
What is a common cause of anosmia
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.
Describe the potential consequences of mid face trauma
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
The piriform cortex is found within the medial temporal lobe. Explain the significance of this with regards to epileptic patients.
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)
Describe the link between Parkinson’s and anosmia
Parkinson’s-anosmia: ?environmental trigger - often early aspects include pathology of the olfactory bulb; initially present with loss of smell and diarrhoea
Summarise olfactory pathways and pathologies
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’
Describe the role of the piriform cortex
•
Pyriform cortex, which processes the discrimination between odours
Where is the orbitofrontal cortex found
Frontal lobe- near the orbital bone.
Ultimately, what is meant by the limbic system
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
What is the limbic system a system of
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.
What are the key functions of the limbic system
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)
State two important parts of the limbic system that are found within the temporal lobes an what circuit are these structures apart of
Hippocampus and Amygdala
Papez circuit
What is the limbic system composed of
Composed of – olfactory bulbs, hypothalamus, amygdala, hippocampus, thalamus and frontal lobe.
Summarise the structure of the limbic system
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
Summarise the papez circuit
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.
What is the function of the Papez circuit?
It is a neural circuit for the control of emotional expression
Describe the pathway of the papez circuit
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
Describe the 3 core parts of the papez circuit
Hippocampus- emotional experience- lays down the new memory
Hypothalamus- emotional expression
Neocortex- emotional colouring
What form of imaging is used to study the limbic system
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
Summarise the hippocampus
Main connections: Afferent: Perforant pathway Efferent: Fimbria/ fornix Functions: Memory & learning Clinical: Alzheimer’s disease, epilepsy
Where can you find the hippocampus on a coronal MRI
The swiss roll structure
Describe the afferent pathway of the hippocampus
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
Describe the efferent pathway of the hippocampus
The efferent is known as the fimbria while the path is attached to the hippocampus, when it leaves, it becomes the fornix.
Summarise the structure of the hippocampus
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
Describe the shape of the hippocampus
Sea-horse shaped
Dentate gyrus and major pyramidal cells joining the two sea-horses
Describe the spatial relations of the hippocampus and the fornix to other important brain structures.
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
Describe the appearance of advanced Alzheimer’s disease on a CT head scan in the coronal plane.
There will be extensive cortical atrophy
The ventricles would appear enlarged
There will also be widening of sulci
Where does pathology associated with Alzheimer’s normally begin
In the transethorinal cortex - first appearance of tangles- appearance of Tau ( a microtubule associated protein- becomes disturbed.
Hippocampus is priamary in Alzheimer’s disease
Describe the microscopic pathologies associated with Alzheimer’s
§ 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.
Describe tau immunostatining
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
Describe senile plaques
Senile Plaques
· Extracellular pathology
· Lumps of protein sitting in between cells in the neuropil
Describe the anatomical progression of Alzheimer’s disease, including the symptoms experienced
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
Summarise the amygdala
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
Describe Kluver-Bucy syndrome
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.
. In Alzheimer’s and Parkinson’s disease, the amygdala starts showing pathology early on. What are the possible outcomes of this?
Patients could either become terrified of everything or they could become totally disinhibited and become quite aggressive
What is important to remember about the brain when looking at it in the coronal view
Note: cannot see horns of ventricles in coronal sections of the brain with the amygdala.
Essentially, what is the amygdala
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.
Summarise Kluver-Bucy syndrome
Syndrome originally described in monkeys with bilateral temporal lobectomy Hyperorality Loss of fear Visual agnosia Hypersexuality
Summarise aggression
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
What are the septal nuclei
The membrane lying between the lateral ventricles anteriorly
Summarise the septal nuclei
Main connections:
Afferent: Amygdala, olfactory tract, hippocampus, brainstem
Efferent: Stria medularis thalami, hippocampus, hypothalamus
Functions:
Reinforcement & reward
(from the nucleus accumbens)
Describe the potential therapeutic use of electrode stimulation to certain parts of the brain
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
Describe the mesolimbic pathway
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
What is important to remember about the mesolimbic pathway
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)
Summarise drug dependence
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.
What effect do all drugs of abuse have on the nucleus accumbens
They all increase dopamine release in the nucleus accumbens
Why do you have to warn the family of patients when prescribing said patient a dopamine agonist
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.
