pheromones

what is a pheromone?

substances secreted to the outside of an individual and received by a second individual of the same species in which they release a specific reaction, e.g a definite behaviour or developmental process (karlson and luscher 1959)

how do pheromones in silk moths work?

• bombykol is a chemical release by female silk moths which acts as a sexual attractant to males

• male mothes can detect bombykol from up to 2km away (very powerful)

• just 5 bombykol molecules can elicit full mating behvaiour in the male

• this shows the extreme sensitivity of the olfactory receptor neurons and the highly tunes behavioural circuitry 

how do mammary pheromones in rabbits work?

• rabbit mammary pheromone = 2-methylbut-2-enal (2MB2)

• female rabbits nurse their young only once a day for 3-5 minutes 

• this means the pups needs to find the nippls very quickly 

• nipples produce 2MB2 that triggers innate behvaioural response for stereotyped nipple search 

• sensed by the main olfactory system

how do sex attractant pheromones in boars work?

• androstenol and androstenone are steroid-derived molecules produced by boars 

• produced in the submaxillary salivary glands so pheromones released into saliva 

• dispersion in air is aided by foaming which helps pheromones evaporate and travel through the air 

• females detect these pheromones and elicit sexual receptivity (lordosis)

• sensed by the main olfactory system

how do chemical alarm pheromones in mcie work?

• 2-sec-butyl-4,5-dihydrothiazole is released when mice are stressed or threatened

• once other mice detect this pheromone they exhibit freezing behaviour

• this is sensed by the grueneberg ganglion

what is a grueneberg ganglion?

• specialised olfactory structure in rodents that detects alarm pheromones 

• located in the tip of the nasal cavity 

• sends signals to the olfactory bulb which relays info to brain areas controlling fear and defensive behaviours 

• causes freezing, avoidance and defensive responses 

• removal of these cells prevents the behavioural response 

what are the different chemosensory subsystems in mammals?

1. main olfactory epithelium 

2. vomeronasal organ 

3. grueneberg ganglion 

4. septal organ of masera

what is the main olfactory epithelium (MOE)?

• sensory organ = olfactory epithelium in nasal cavity

• function = odour detection

• target = main olfactory bulb

what is the vomeronasal organ (VNO)?

• sensory organ = vomeronasal organ in nasal septum

• function = pheromones, social/sexual signals

• target = accessory olfactory bulb

what is the grueneberg ganglion (subsystem)?

• sensory organ = tip of nasal cavity 

• function = alarm pheromones, predator ordours, cold 

• target = main olfactory bulb (necklace glomeruli)

what is the septal organ of masera?

• sensory organ = small patch in nasal septum 

• function = general odours 

• target = main olfactory bulb

what are necklace glomeruli?

• specialised golmeruli in the main olfactory bulb

• receive input from specific sensory neurons (e.g guanylyl cyclase-dependent OSNs and the grueneberg ganglion)

• target strcture within the main olfactory bulb that process certain pheromones

what are guanylyl cyclase-dependent OSNs?

• typeof olfactory sensory neurons that use guanylyl cyclase signalling instead of the usual cAMP pathway 

• detects specific cues like alarm pheromones, predator odours and some pheromones 

• part of the MOE and grueneberg ganglion 

what are the three main families of receptors in the VNO?

1. vomeronasal type 1 receptors (V1R)

2. vomeronasal type 2 receptors (V2R)

3. formyl peptide receptors (FPR)

what are V1Rs?

• found in upper (apical) layer of VNO sensory epithelium

• G-protein coupled receptor to Gαi2 protein

• detect small, volatile pheromones 

• mediate reproductive and social behaviours (mating and aggression)

what are V2Rs?

• found in lower (basal) layer of VNO sensory epithelium

• G-protein couples receptor to Gαo protein

• detect larger, non-volatile peptides and proteins

• mediate individual recognition, terrirotial marking and predator cues

what are FPRs?

• some vomeronasal neurons express FPRs

• detect pathogen and inflammation related molecules 

• can trigger defensive/avoidance behaviours 

what is the flehmen response?

• behaviour seen in many mammals characterised by curling of the upper lip, raising of the head and sometimes opening of the mouth 

• flehmen posture allows muscles of VNO and aossiated blood vessels to expand and contract which creates a uction effect to draw in fluid or air ocntaining pheromones into the VNO

• blood vessels around VNO act as a cardiovascular pump as VNO lumen opens and closes 

• detects sex pheromones to rrrigger mating behaviour and social pheromones 

what happens when there is VMO deficits?

• TRPC2 knockout = loss of male-male aggression

• instead males showed sexual behaviour towards both males and females 

• females lacking TRPC2 failed to shownormal aggressive resposes toward intruders when nursing 

• shows that sensory activation of the VNO via TRPC2 is essential for sex discrimination in mice as phermone-based cues are necessary to tell males from females

what are signature mixtures in mouse pheromones?

• unique combinations of chemical signals- mainly urinary volatiles and major urinary proteins that allow individual mice to recognise each other

• volatile pheromones like 2-sec-butyl-4,5-dihydrothiazole are quickly detected by VMO or MOE

• majory urinary proteins are proteins secreted in urine that bind to volatile pheromones

• each mouse produces a slightly different mixture of volatiles and MUPs so other mice can tell who it is e.g certain pheromones are sex specific 

• this allows recognition, identification and communication of social information

what are the key features of MUP and bound ligand complexes>

• long-lasting signal as MUP-bound pheromones evaporate slowly

• signal individuality = signature mixture 

• elicit countermarking = maintains territorial boundaries 

• freshness of marks = ratio of volatile and non-volatile components may indicate how recent thr mark is which allows mice to judge the age of a territory mark

what is ESP1?

• exocrine gland-secreting peptide 1 

• produced in male mouse tear fluid (lacrimal glands)

• protein based pheromone (not volatile)

how does ESP1 cause lordosis in female mice?

• female mice exposed to ESP1 showed lordosis behaviour even without other cues 

• demonstartes ESP1 pheromone directly activates females sexual response 

• detection occurs via VMO through V2Rs 

• signal sent to accessory bulb then to hypothalamic and limbic areas that control mating behaviour 

what are the mechanisms of vomeronasal transduction?

• normally a pheronome binds to V1R or V2R receptors in VNO neurons and G-protein signaling activates TRPC2 channels

• calcium influx depolarises the neuron and this sends signals to the accesory olfactory bulb

• if there is TRPC2 knockout however, there are alternative intraveccular signalling paths

• pheromone binds to receptor = G-protein signaling stimulates phospholipase C (PLC) to produce inositol trisphosphate (IP3)

• IP3 binds to receptors on ER which releases calcium from intracellular stores to partially depolarise the neuron

• this shows not all VMO signaling relies on TRPC2 and how knockout can still show limited pheromone detection

what is the difference between V1R expressing VSNs and OSNs?

• VNOs detect pheromones and social chemical cues not general odours and this is responsible for innate behaviours like mating

• VSNs can detect very low concentrations of pheromones and this sensitivity is much higher than the MOS which detects general odours at higher concentrations

• each V1R expressing neuron is tuned to a very specific, small, volatile pheromone = one neuron to one pheromone to ensure precise detection of social/sexual cues

V2R VSNs and MHC peptide ligands

• MHC (major histocompatibility complex) molecules are involved in human system function

• peptides derived from the MHC are released in body fluids like urine 

• V2R VSNs detect peptide based cues, particularly MHCs to enable genetic and social discrimination

do human sexual attractant phermones exist?

• human sense of smell has declined as visual and verbal communication have become more important

• human behaviour is so complex that it is difficult to identify definite responses

• but individuals do have a personal odour that is likely to vary with hormone levels and that can be learnt

• no good scientific basis for sex attractant pheromones in humans.