BIOL 2052 - Chemical senses

general features of sensory systems

• response to environment which are important in determining mood and behaviour

• geneally: transmission —> encoding —> processing

chemosensory receptors

CHEMOSENSORY RECEPTORS (exteroceptors)

• receptors that generate a signal when they bind to chemicals in the external environment

• chemosensation one of the oldest senses —> evolutionarily conserved

  • olfaction: info about airborne molecules

  • gustation: info about ingested substances (chemical and physical qualities)

• lower organisms sensory systems good for seeking and avoiding behaviour

• in higher organisms like us: chemical senses allow us to:

  • stimulate GI system

  • asses quality of food

  • determine if nutritionally beneficial

distance chemosensation

• can sense ethanol at 2mM

• 2 trans-6-cis nonodenial (found in cucumbers) 0.07nM

• interpretation of smell can be concentration dependent due to the patterns of neural circuitry (some in mM range, some in nM range) —> indole perfumes putrid at high concs

• detection of natural odours is detection of a combination of molecules

• olfaction is a reflection of the pattern of diff cells that are actiavted by the diff molecules interpreted at higher centres of the CNS

olfaction

• smell comes in through the nostril —> nasal cavity

• olfactory epithelium found in the nasal cavity and is a structure which houses olfactory neurons

• ORN which have cilia which directly engage with the external environment

• ORN travel through channels in cribiform plate —> olfactory bulb —> brain

• anosmic = no ability to smell

olfactory epithelium

• bipolar neurons

• projection to olfactory bulb at the surface of the nasal cavity where the cilia lie

• unmyelinated —> not too far to travel to the brain

• cilia is embedded in the mucous layer which is produced by Bowmanns gland

• mucous responsible for concentrating the chemicals and bringing them in contact with cilia

• these neurons are succeptible to damage

• replenished by STEM cells roughly every 6-8 weeks

• STEM cells located in the epithelum

how are odours transduced

• response to when the odour is applied to the cilia as opposed to the soma is a much larger response —> cilia have transduction proteins which respond to smells

• transduction occurs via GPCRs —> evolutionary conserved and encoded for by 3-5% of the genome

• variation in the AA structure of GPCRs allow detection of diff molecules

• each neurone will express 1 GPCR

• selective distribution of GPCRs in diff areas of the nasal epithelium —> 17 GPCRs in one region, M71 GPCR expressed in diff regions

signalling pathways

• G protein coupled to GPCR called Golf

• activated GPCR —> activation of adenylyl cyclase —> increased cAMP

• increased cAMP acts as a 2nd messenger which activated cyclic nucleotide gated channels

• calcium and sodium move into the cell which causes depolarisation of the cell

• some pathwys where calcium can cause chloride to move out of the cell and aid depolarisation

encoding of olfactory signals

• individual ORNs are sensitive to a subset of stimuli

• graohs below show the response of ORNs to smells —> neuron 1 the only one that responds to all 3, neuron 2 the only one that responds to the first one

• this is how information is encoded

across fibre pattern coding

• each neuron has a certain no of molecules required to activate it

• this will differ for the carbon chain length and for the neuron activated which allow for further encoding

• coding info across a population of neurons and depending on the output wil determine what it is (across pattern coding)

• this allows us to encode natural odours to distinct patterns across a number of neurons which allows the scent to be indentified

• realistically there are lots of compounds in natural odours but we only maximally respond to a few of them

• E,g: indole —> at low concs it activated a certain pattern of neurons bit activates diff neurons at high concs

structure of the olfactory bulb

• glomeruli: spherical structures below the surface of the olfacotory bulb —> regions where synapses made between the receptors and the mitral cells

• mitral cells - send projections down the glomerulus which forms synapses with ORNs

convergance and amplification

• all neurons which converge to the same glomeruli express the same GPCR

• bilateral pattern

• single glomerulus can have dendrites from 25 mitral cells and recieve inputs from 25,000 olfactory cells

molecular endocoding and electrical patterns

• signals from teh olfactory bulb —> accessory nuclei

• the relationship between one type of odourant neuron and one glomeruli enables specific regions of the olfactory bulb to respond to diff chemicals

• diff odours and chemicals will activate a unique spatial pattern in the olfactory bulb depending on their chemical composition

• chemically distinct single odourants will maximally activate one or only a few glomeruli

processing olfactory signals

• signals from the olfactory system travel through cranial nerve 1 —> olfactory bulb where they project to cortical structures

  • piriform cortex (has no clear pattern of organisation like the sensory cortex)

  • olfactory tubercule

  • amygdala

  • entorhinal cortex

• signals from there —> other structure like the hippocampus

  • this is how smell can impact mood or trigger memory

• its different to other sensory systems as it doesn’t go straight to the thalamus —> goes via the olfactory bulb targets and olfactory cortex

gustation

• is an example of contact chemo sensation —> must come into contact in order to taste something

• tongue is the main sense organ

• 4 types of papillae (invaginations) on the tongue with different number of taste buds (house the gustatory receptors)

  • circumvallate located at the back of the tongue —> 250 taste buds

  • foliate at the sides —> organised into parallel ridges with 600 taste buds

  • fungiform at the front —> 3 taste buds

  • filiform in the middle

• apart from filiform all have associated taste

circumvalate papillae

• troughs fed by serous gland which secretes saliva

• taste buds at the base of the trough

• saliva breaks down food in the mouth and concentrates down the moleules for taste buds

5 basic tastes

• bitter (caffiene, nicotine)

• sour (actetic acid)

• sweet (glucose, fructose)

• salt (NaCl)

• umami (Msg)

• all in the millimolar range —> less sensitive than smell

• sensitive to bitter, can respond at low concentrations

• less sensitive to glucose —> nutritionally beneficial so drives our sense to consume more of it

• sensitivity range: bitter>acid> salt> sweet

• certain regions of the tongue are more sensitive than others —> driven by expression levels of receptors

• can be advantageous —> bitter at the back —> drives a pathway to spit out the food

• some selectovity of regions where certain tastes initiate activity

taste buds

• a single taste bud can contain up to 50 specialised epithelial cells which convert checmical —> electrical signals

• the tips of the cells have microvilli which increase the surface area and come together at the taste pore

• receptors are localised in the microvilli

• olfactory receptors neurones are bipolar neurons, however, gustatory system receptor cells release neurotransmitters whcih cause signalling in the afferent neurons

• taste cells are subject to damage - require basal cells to regenerate them

transduction in taste cells

• apiccal domain where receptors expressed

• ion channels and GPCR depending on taste

  • salt/sour - ion channel

  • sweet/bitter/umami - GPCR

• influx of Na leads to opening of voltage gated Ca channels and influx of Ca which causes the release of serotonin and ATP

• signals are returned via 3 cranial nerves

  • vagus (10)

  • facial (7)

  • glossopharangeal (9)

salt/sour sensing

SALT

• Na ions move down their conc grad through amilloride sensitive ion channels

ACIDS

• H+ sensitive ion channels

• H+ ions block K+ channels which prevents K+ from leaving and results in depolarisation which opens voltage gated Ca2+ channels

• direct depolarisation results in no second messenger

sweet/umami sensing

• T1R heterodimers

• lots of variation in AAs

• ligands that bind depends on the heterodimer

SWEET

• T1R2/T1R3 signals through G protein which activates PLCB2 which activates IP3

• engages with eR receptor and release of Ca

• activation of TRPM5 Ca ion channel —> depolarisation

• this is an indirect response to depolarisation

• 

UMAMI

• diff heterodimer - T1R1/T1R3

• same pathway as sweet

• has another signalling pathway of the GluR4 - also an mGluR4 receptor in brain with a longer N terminus

• inhibits cAMP signalling (diff pathway)

• 

bitter sensing

• T2R receptors (GPCRs)

• 25% of population dont respond to it (phenylthiocarbamide)

• diff populations of taste cells as T1R

• shorter N terminal

• signalling via IP3/Trpm5 pathway

• specific to G protein alpha gusducin, only expressed in bitter taste cells

downstream signalling

• determined by rodent knockouts (of the TrpM5 Ca2+ ion channel)

• sweet and umami have a positive correlation as conc increases quinine/bitter has a positive response

• TrpM5 have a phospholipase B important signalling for sweet umami and bitter

processing

• 3 cranial nerves return signals from diff parts of the brain

  • 7: tongue pallate —>nucleus of solitary tract (gustatory nucleus)

  • 9: back of the tongue —> medial region of the gustatory nucleus

  • 10: eppiglottis/oesophagus —> caudal region of the gustatory nucleus

• these are the 1st order neurons

• medulla —> thalamus and other parts of the brain

• the nucleus of the solitary tract intergrates visceral info about gut motility (as gut innervated by vagus nerve)

• drives gustatory visceral reflex arc —> enables you to be sick if you consume something bad tasting

• from the gustatory nucleus in the medulla the ventral posterior medial nucleus of the thalamus

• signals from the thalamus go to:

  • amygdala

  • orbitofrontal cortex - 2ndary taste centre

  • insula

mapping of gustatory cues

• some mapping that takes place

• some regions particularly sensitive to NaCl compared to sweet/bitter

labelled line coding

• gustatory system uses labelled line coding

• in mice, experiments undergone where a wild type and a T2R knockout exposed to a taste and response recorded

• the response in t2R knockout much lower than wild type

• T2R gene in knockout turned back on to see if wild type response cen be rescued

  • only in mice exposed to glutamate is response restored

  • this means that only cells which express T2R receptors only respond to bitter taste

• orbitofrontal cortex gives our overall perception of food

  • involved in satiation - as we become satiated, signalling in orbital cortex decreases