Olfaction, Neuropeptides and Behaviour Flashcards
How are pheromones detected?
Via the vomeronasal organ in the nasal septum. VNO sensory neurons project to ACCESSORY OB and from there to the AMYGDALA and HYPOTHALAMUS via the OF tract
What are the 3 principle cell types in the olfactory epithelium? What are their key features?
Olfactory receptor neurons:
- Bipolar shape
- Dendrite with cilia hairs coming off
- Site of OF transduction
- Penetrate the CNS
Basal cells:
- Like a stem cell, is the source of new receptor cells
- Needed as nasal epithelium are turned over every 4-6 weeks
Supporting cells:
- Act like glia, physically supporting receptor cells
- Provide protective mucus with antimicrobial and odorant binding properties
How is odour detection transduced (molecularly)? (Jones and Reed)
- GPCR in the OF epithelium called Golf
- Causes increase in intracellular cAMP
- Opens calcium channels (depolarises the cell) and chloride channels (sustains activation)
What did Buck and Axel DO?
- They identified a large GPCR gene family of ~1000members, and that they were expressed in the nasal epithelium- potential odorant receptors
- Axel studied catfish
- Used an in situ hybridisation to analyse receptor expression in the catfish olfactory epithelium
- They found that each individual receptor gene is expressed in sensory neurons within a given spatial zone (i.e., in specific areas)
- Axel essentially took the G[olf] promoter made it express Tau-LacZ, a protein that produces axonal beta-Galactosidase that can be visualised by a colorimetric assay (dyed blue)
- They visualised the innovation of the OB by neurons from the OF epithelium
What is allelic exclusion?
Receptor neurons only expressing one type of receptor protein
Why did Axel use Tau-LacZ rather than just LacZ?
Tau allows LacZ to innovate neurons
Receptor neurons expressing one type of receptor project to a small number of (USUALLY 1) glomeruli, even when they are spatially separated.
With what cells do receptor neurons synapse with in glomeruli
Mitral cells
How is a spatial map of olfaction maintained when cells turn over every 3-4 weeks? (Wang et al)
- Inducing death of neurons expressing one type of receptor
- When reintroduced, these neurons innovated the SAME PLACE and SAME GLOMERULUS of the OB
- They found projections from the OFE found the rough area on the OB but the receptor on the surface was required to establish specific connectivity
- Each glomerulus responds only to the chemicals that activate a specific receptor
- Swapped M1 and P2 receptors genes - neurons went to completely different places (not where the other receptor goes. So dependent on environment, not just receptor)
What is the idea behind population coding of smells? What was used to study this and why?
What was studied?
- Drosophila as 80 receptor genes
- Sensory receptors project to one glomerulus
- Used Ca2+ reporters to map glomerular activation
Findings:
- You get grades of coding from different glomeruli from a single odour
- Smells are made up of composite odours that interact with multiple receptor types
- Ratios of glomeruli activation determine the smell perceived
What is the nuance of spatial coding in olfaction?
- Glomeruli that detect chemically similar odours are grouped closer together
What are trace amine odours?
- Small family of GPCRs coupled to Golf
- More related to biogenic amine receptors than OF receptors
What are the 2 types of TAAR and what are their functions?
TAAR4:
- Sensitive to 2-Phenylethylamine
- Which is in carnivore urine, lions, tigers, jaguars have 1000 fold this
- Related to avoidance evolution
TAAR5:
- Sensitive to trimethylamine
- Sexually dimorphic, males have large amounts in urine which is attractive to females
- Positive attractive quality is fully mediated by TAAR5
What is the formula for the perfect social signal?
cheap to transmit, cheap to receive, discreet, selective, long-range, long-lasting, easy identification
What is chemosensation
- Traditionally a sense of smell detects volatile compounds for identification of substances that may be beneficial of harmful
- Male selection in sexual reproduction
- Essential impetus for evolution
What is the Proust effect
Smell can be used to recall memories better than other senses
What is the definition of a pheromone?
Any chemical signal conveying information between members of the same species (usually eliciting a particular behavioural or physiological change)
What are common uses of pheromones and what are the two types?
- Health, mate choice, incest avoidance, sexual maturation, aggression (locusts) territory marking (dogs), dominance (wolves)
Two types:
- Releaser pheromones: Immediate effect
- Primer pheromones: Long term, e.g., puberty
What is bombykol
- First isolated pheromone
- Discovered by Germans studying silkworm moths
- Sense organs were on the antennae of moths
What are 2 examples of releaser pheromones?
Alarm pheromones:
- Some species release when attacked by predator to warn same species
- aggregation of locusts
Trail making:
- Leaf-cutter ants lay pheromones to mark the trail to a food source
The VNO projects to the accessory OB. Where is this information then relayed?
Amygdala and Hypothalamus
Due to anatomical connections, organism may not be conscious of effects
Not detailed, but what does cranial nerve 0 do?
- Structure of the accessory nasal system
- Secretes gonadotrophin releasing hormone which effects reproductive endocrinology
Match the Effect to the Description:
a) Pregnant mice exposed to novel male spontaneously abort, followed by mating with novel mouse
b) Re-mating with arrival of new potential mate
c) These female mice will eventually become anoestrous in the absence of males. If a male is introduced, the females will start to cycle synchronously within 3 days. Females cycling together have higher chance of offspring survival
d) Female mice housed together in small groups in the absence of males exhibit prolonged dioestrous that is maintained by progesterone secretion from the corpora lutea
e) Female rodent pups undergo puberty earlier if males are present than if males are absent, isolated female mice go through puberty later than when raised with other females due to pheromones
- Lee-Boot effect
- Whitten effect
- Vandenburgh effect
- Bruce effect
- Coolidge effect
a) Bruce effect
b) Coolidge effect
c) Whitten effect
d) Lee-Boot effect
e) Vandenburgh effect
What is the major histocompatibility complex (MHC), and why is it?
- MHC genes code for special protein markers that attach to a cell and help recognition of intruders
- Different MHCs recognise different intruders
- Advantageous for mother to select a mate with different MHCs
- Evolutionary drive
Most of the studies have studied animal pheromones.
What evidence is there for/against human pheromones?
FOR:
- Dogs can detect bladder cancer from human urine due to alterations in odorants caused by MHC changes in oncotic cells
- Androgen-based volatile steroids have MHC constituents
- Hypothesised that humans are able to detect pheromones via the MAIN olfactory system rather than the accessory OF system
- PET scan of brain found that we do respond to pheromones in a sexually dimorphic manner
- Synchrony of menstrual cycles among women thought to be due to pheromones
AGAINST:
- Humans do have a VNO but is thought to be non-functional
- VNO signal and receptor genes are pseudogenes in humans
Human pheromone detection is thought to be sexually dimorphic
What are two compound that elicit different responses in men/women
AND - Hypothalamic activity in women, not in men
EST - Thalamic activity in men not women, present in human sweat
What are the two types of EFFECTS of sex hormones? Examples
Organisational effects
- During development
- E.g., the sexually dimorphic nucleus of the medial preoptic area
Activational effects
- Effects of circulating hormones
What is Guevedoces?
- Condition in which patient has XY chromosomes but don’t have testosterone during the developmental period
- Specifically, mutation leads to no production of dihydrotestosterone
- At puberty, peripheral tissue produces secondary sex characteristics
- Symptoms - ambiguous genitalia
Advantages of monogamy
- When it takes 2 to raise a family; predation / resources
- Hard to find a partner
- Examples: angler fish, prairie voles
- Evolved by tweaking mechanisms that promote maternal bonding
Discuss the following about oxytocin:
a) Function
b) Life cycle
c) Oxytocin KO mice
d) Mating and oxytocin
a)
- Promotes uterine contraction during labour
- Milk ejection during lactation
- Maternal nurturing and bonding post-partum
b)
- Synthesised in the hypothalamus, axons project to posterior pituitary where it is released directly into the blood stream
- From here it acts on the uterus and ovaries
- Also released IN the brain
c) Oxytocin KO mice have social amnesia (social interaction time (sniffing) decreases)
d) Mating stimulates huge OT release - involved in partner preference formation (examined in prairie voles OT injections / antags - cuddling time)
What is different between men and women in the medial preoptic area (MPA)?
- Sexually dimorphic
- Males have more androgen receptors present in MPA compared to females
- Treating females with OE or androgen increases receptor number - turns into male look-alike brain region
- I.e., is mediated by androgens
How do prairie voles and meadow voles differ? (behaviourally and molecularly)
- Prairie voles highly social, monogamous, biparental
- Meadow voles solitary, promiscuous, uniparental
- P-voles have high concentrations of OT receptors in the Nucleus Accumbens
- Meadow voles have very low OT receptor conc throughout the brain
What is the role of Vasopressin
- VP plays important role in pair bonding in prairie voles
- Similar structure to OT
- Important in territorial behaviour, scent marking, aggression, pair bonding
- VP injection into meadow voles increased pair bonding and preference time
What is the chemistry of pair bonding in terms of NTs/Hormones?
- OT and VP: Perception of social stimuli, KO mice have social amnesia
- DA: Reinforcement
- Opiates: Hedonic
Outline the role of dopamine in pair bonding
- D1 and D2Rsheavily expressed in the CAUDATE PUTAMEN and NUCLEUS ACCUMBENS
- D2R antagonist blocks pair bond formation after mating - D1R antag doesn’t
Outline role of opiates in pair bonding
- Morphine antagonists block pair bonding
How might early life experience effect social behaviour?
- Early life separation/stress impairs pair bonding in females in later life
- Low OTRs in the NucAcc confers susceptibility to IMPACT of early life stress on social cognition (Low OTRs = Less pair bonding)
- Lower OT CSF conc in women with history of childhood abuse
How did researchers examine sadness of voles when looking into separation anxiety
- Water test
Tail hanging test
What is the role of corticotrophin releasing factor (CRF) in social loss
- CRFR2 is colocalised with OT
- CRD R2 agoninst supresses OT release in the NucAcc, antagonist increases
- Interaction of CRFR2 (in NucAcc) and OT mediate the emotional consequences of partner loss
- Chronic CRFR2 activation leads to aversive emotional state: bereavement
What are the parallels of OT and VP expression in humans
- OTR patterns correlate with activation of brain regions in humans
- Genetic variation in the VPR1a gene (AVPR1a) associates with pair bonding, and in OTR gene
- OT increases trust in humans
Describe the role of mitral cells in the olfactory system
- In the OB there is a mitral cell layer responsible for OUTPUT
- After olfactory receptor cells from the nasal epithelium reach glomerulus, mitral cells form dendro-axonal connections on them
- Mitral projections run along lateral olfactory tract to a relay station - the Anterior Olfactory Nucleus (AON)
- From the AON, run to the Anterior Periform Cortex (APC) where info is stored
What type of neuron is VP expressing? How did they find this out?
- External Tufted (ET): Glu
- GFP expressed under VP promoter, attached to VP in vesicles
- Stained periglomerular (PG), external tufted (ET) and short axon (SA) cells for different neurotransmitters to workout what cell types they are
- Glutamate is expressed in VP cells
- VP neurons project to mitral and granule cells (intrinsic OF system)
What is the difference between an anterograde and retrograde tracer?
Retro - Inject where synaptic terminals are, transported back to cell body and stain
Antero - inject where cell body is, will be taken to terminal
How was it found that VP neurons
a) Do not project outside the OB
b) Do not express V1aRs / any VPRs
a)
- Viral transfection of rAAV-based targeting VP neurons
- Venus marker fills cytoplasm so stains axons + dendrites
- Could be used as retro and anterograde tracer
b) VP cells do not express VPRs, so must function somewhere else
What is the role of VP in the OF system?
Inhibits basal mitral cell activity:
- slows firing rate
- VP decreases how long cells are active for
Inhibits odour stimulated mitral cell activity:
V1R antagonist prevents social recognition
What is the use of diptheria toxin in OF systems
- Selectively destroys VP cells
- Does this by becoming internalised by binding to diptheria receptor and triggering cell death
- Diptheria receptors only expressed on cells that have VP promoter - so only on VP cells
- Diptheria therefore prevents social recognition
How was small interfering RNA (siRNA) used in the study of VP?
- siRNA against V1Rs - blocks transcription of RNA and blocks production of Rs
- siRNA against V1aR: VP signalling loss removes social habituation, but not to other scents
Outline the role of VP in first exposure / priming in the OF system
- In the MAIN OB, upon first exposure to a scent, very little VP is actually released from dendrites.
- Either a s a late response to this activation, or as a response to a recurrent signal from the AON, these neurons now become primed (VP vesicles mobilised for activity)
- In response to re-exposure to the same OF fingerprint, mobilised VP is released and BLOCKS mitral cell activation
- This works to filter out recognised social stimuli
- This facilitated recognition if then translated to a reduced investigation time for familiar conspecifics (same species)
Where is VP found and what is its function in each place?
Main OB:
- Appears to be a retrograde signal that filters activation of mitral cells
Anterior Olfactory Nucleus:
- Involved in processing social odour cues
Accessory OB
