Lecture 4 - Chemical senses (Olfaction)

what is sound related to?

• intensity

• frequency

what is light related to?

• location

• intensity

• wavelength (colour)

labelled line

• each sensory neuron is dedicated to one specific stimulus

• specific neuron responding to only one stimulus

• particular sensory perception and there’s a dedicated neural channel for that perception

  —> specific neural channels dedicated for that perception

combinatorial code

• many neurons fire together in response to a stimuli

• particular sensory stimulus that is encoded by multiple neurons - a population of neurons

• each neuron responds differently to different situations

Basic Mechanism of Olfactory Transduction - the way a single odorant molecule gets turned into an electrical signal that travels to the brain

• this mechanism has to do with how a single odorant molecule is turned into an electrical signal that travels to the brain (triggering a nerve impulse)

1. Odorant is detected - an odorant molecule reaches the olfactory epithelium and binds to a specific G-protein- coupled olfactory receptor on the cilia of an olfactory sensory neuron

2. The binding changes the receptor’s shape and activates its attached G-protein (Golf)

3. Activated Golf then activates adenylyl cyclase

4. Adenylyl cyclase converts ATP into many cAMP molecules

5. Rising cAMP binds to and opens cAMP-gated cation channels - letting Na+ and Ca2+ flow into the cell

6. The incoming Ca2+ opens Ca2+-activated Cl- channels, Cl- exits, enhancing depolarisation

7. The combined ion movements depolarise the neuron to threshold (makes the inside of the cell positive enough to hit its trigger voltage which starts an action potential)

8. The neuron fires an action potential that travels through the olfactory nerve to the brain’s olfactory bulb

are different olfactory receptors specific to different odorants or not?

• the different olfactory receptors are specific to different odorants

• each olfactory receptor responds to a unique profile of odorants

Experiment done on Drosophila to support the idea that different olfactory receptors are specific to different odorants (Hallem and Carlson) :

• removed the natural olfactory receptors from Drosophila

• artificially placed olfactory receptors in one specific neuron

• took electrical recordings from that neuron

• then presented a panel of different odours to record how the particular receptor responds to different odours

  —> example, receptor Or7a responds most to E2-hexenal whereas receptor Or10a to methyl salicylate

  —> each olfactory receptor has a particular profile of odours that it will respond to

Single-cell whole transcriptome sequencing (Hanchate et al.)

• as olfactory sensory neurons mature - they narrow their gene expression down - to express a single olfactory receptor each

• shows that at the beginning when neurons are immature they start off by expressing lots of different receptors - but over time as they mature - 1 receptor takes over and cancels out the expression of all other receptors through negative feedback loops

The pathway of sensory neurons transferring information to second-order neurons at glomeruli in Drosophila:

Drosophila (fruit fly)

• Olfactory receptor neurons (ORNs) detect odour

• their axons enter the antennal lobe

• ORNs with the same receptor meet in one glomerulus

• In that glomerulus they excite second-order neurons:

  projection neurons (PNs) - carry signal out

  and

  interneurons:

  local interneurons - give lateral inhibition

• PNs send axons to mushroom body and lateral horn

• so the sensory neurons transfer information to second-order neurons - which then carry the infro from the glomeruli into higher brain centres

The pathway of sensory neurons transferring information to second-order neurons at glomeruli in Mammals:

Mammals

• Olfactory sensory neurons (OSNs) in nose detect odour

• Axons bundle as olfactory nerve to the olfactory bulb

• OSNs with the same receptor join one glomerulus

• In that glomerulus they excite second-order neurons:

  mitral and tufted cells (projection)

  and

  interneurons:

  periglomerular and granule cells (inhibition)

• mitral/tufted axons form the lateral olfactory tract to:

  piriform cortex, amygdala/tubercle, hippocampus

what does receptor specific matching of sensory neurons to second-order neurons ensure?

ensures that odour specificity is carried through

where do second order neurons carry info from and to?

second order neurons carry the information from the glomeruli into higher brain centres

second order neurons rceive input from only one glomerulus to maintain specificity

what are the key computations carried out in the first olfactory relay in early olfactory information processing?

• adaptation

• reducing noise

• gain control

• de-correlation

• lateral inhibition

Adaptation at the synapse

• there’s synaptic adaptation that emphasises the start of the odour

• allows the nerve system to focus on changes in odours

Converging sensory neurons onto second-order neurons

• reduces noise

• strengthens weak responses

• allows the second order neurons to integrate and average together the activity of lots of sensory neurons

what are the functions of the lateral inter-glomerular cross-talk?

1. gain control - neurons to be sensitive to both very weak and very strong odours

2. de-correlation - make responses of neuronal population to different odours as different as possible

what are odours detected by?

olfactory sensory neurons

all the sensory neurons that express the same receptor converge on what location?

glomerulus

the second order neurons receive input from what?

a single glomerulus

what does the synapse between the sensory neurons and the 2nd order neurons transform?

transforms the ododur code to emphasise the start of the odour

reduces noise does what?

amplifies/strengthens weak responses

the local neurons between the sensory neurons and 2nd order neurons carry out what?

gain of control

• to tell apart both weak and strong odours

de-correlation

• seperate out different odours

What are the kinds of higher olfactory behaviour that the different areas of the brain regulate?

• learned behaviour (what is picked up)

• innate behaviour (born knowing how to do)

where does learned behaviour/responses happen in humans?

cortex (piriform)

where does innate behaviour/responses happen in humans?

amygdala

where does learned behaviour/responses happen in insects?

mushroom body

where does innate behaviour/responses happen in insects?

lateral horn

experiment showing cortical amygdala is require for innate odour responses (Root et al.)

• mice are afraid of predators

• the experimental odour is TMT = an odour specific to foxes

• mice are placed in a behavioural arena and put the fox odour in one of the quadrants

• blue line seen indicates the tracks of the mice

• mice avoids the smell of the foxes = mice spent less time in the odour quadrant

• then an optogenetic silencer is used to silence the cortical amygdala

• and then use an optical fibre to shine a light into that part of the brain

• it prevents the behavioural response = so mice don’t avoid fox odour anymore

TMT = less time spent in quadrant

Silencer + optical fibre = equal amount of time spent in each quadrant

—> this shows that specific region is required for certain behaviour and when blocked the behaviour changes/doesn’t happen

state the differences between innate vs learned circuitry

purpose

• innate - categorise

• learned - discriminate

activity

• innate - dense

• learned - sparsely

what odours?

• innate - certain preferred

• learned - arbitrary —? respond to any odours

connectivity

• innate - stereotyped

• learned - random

strategies for innate behaviour

hardcoded rules, FSM, genetic code

—> fixed, automatic, unchanging

strategies for learned behaviour

supervised, reinforced learning, neural networks

—> flexible, adaptive, experience-based

what does taste transduction use?

• metabotropic and ionotropic receptors

• metabotropic receptors can be used to amplify signals

key taste circuit

1. taste information comes into the tongue through cranial nerves (taste buds)

2. taste information then goes into the brain stem to the part of the brain called the solitary nucleus

3. this then goes to the ventral posterior medial nucleus (VPM) and the thalamus

4. then to the insula and parietal cortex

lateral inhibition on taste (Chu et al.)

(fruit-fly experiment)

• bitter and sweet sensing neuron

• bitter sensing neuron activates GABAergic inhibitory interneuron - which releases GABA onto postsynaptic terminals of the sweet sensing neurons

• so when the bitter and sweet are tasted at the same time the bitter taste will directly inhibit the sweet taste - so fly won’t want to keep eating it