Olfaction and Social Recognition in Rodents Flashcards
What are the differences between the main and accessory olfactory systems?
Main Olfactory System
Detects volatile compounds
Pathways project from the olfactory bulb to the amygdala
Responds to a wide range of social and non-social cues
Accessory Olfactory System (VNO) Detects non-volatile compounds Pathways project to the amygdala Detects socially relevant non-volatile cues Sexually dimorphic
What is the importance of olfaction in social recognition?
- Rodents depend to a considerable extent on olfactory pathways
- Olfaction is a predominant source of information necessary for social recognition
- Strange males attacked and commonly killed by resident males.
- The ability of individuals to identify members of their own species and distinguish between the sexes is crucial for social behavior
- Social recognition is necessary not only for social living, but also coping with costs of social behavior eg) increased risk of exposure to parasites and infection.
- Animals use social information, including that provided by chemical signals.
What are the different types of chemical signals?
Volatiles → sex and social status
• Urine of male mice contains specific, small volatile organic compounds under androgen control
• These compounds provide information regarding reproductive and social status, and are attractive to females at a distance
Volatiles → kin from non kin &condition
• MHC- associated urinary cues
• Used in mate choice, determining kin from non-kin, recognizing familiar individuals
• Also used for determining age and condition → used as indicators of health, disease and immune status of an individual.
− Alterations in these urinary MHCs related to changes in immune activity associated with infection.
Non-volatiles → individuality
• Major urinary proteins (MUPs)
• Made in the liver under stimulation by androgens, concentrated in urine
• Used for recognition of individuals.
Describe the structure of the VNO
Rodent VNO
• Enclosed in a cartilaginous capsule
• Sensory epithelium located medially
• Changes in blood flow to the VMN change volume and pump stimuli in and out
An intact VNO is crucial for many key behaviours in mice:
Effect of VNO ablation:
• Male sexual behavior directed to females → reduced, fewer mounts
• Male sexual behavior directed to males → none reported
• Male ultrasonic vocalization to females → reduced/eliminated
• Male ultrasonic vocalization to males → reduced/eliminated
• Male aggression to intruder male → eliminated
• Maternal aggression to intruder male → eliminated
Projection of VNO Pathways
• Projects to amygdala
• V1 and V2 receptors have very different structures (and probably functions) and output from the VNO sensory neurons is processed separately in the accessory olfactory bulb AOB, but then neurons converge to common sites in downstream targets.
VSN neurons:
• Class 1 are specific, class 2 may be more general
• Project to different areas of the AOB
• Most sensitive mammalian chemoreceptors
• Highly selective for specific compounds
• Detect pheromones
How are pheromones classified?
- Karlson and Luscher define pheromones as → 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, eg, a definitive behavior (releaser pheromone) or a developmental process (primer pheromone).
- Releaser pheromones → single or few molecules which elicit dramatic behavioural effects
- Primer pheromones → cause longer term effects on neuroendocrine or developmental pathways
eg)
• Nipple search pheromone in rabbit is a single molecule (2-methylbut-2-enal)
• The androgen pheromone in boars is composed of 2 compounds (androstenol and androstenon). This controls attraction and standing response in female pigs.
• A complex range of compounds are involved in puberty acceleration and estrus induction and syncronisation in female mice.
Boar Releaser Pheromones
• Knowing non-heat and heat behavior makes it easier to identify which female is coming into heat, and when they reach sanding heat (which is when breeding ideally occurs) → the female will lock up and stand rigidly, to be receptive to mounting of a boar
• In the days prior to standing heat, female may or may not present signals that heat is coming
• Applying pressure to the back of the animal to see if she will stand rigidly is the most common manner to check for standing heat
• Having an active, mature boar to check with heat checking is the best way to determine standing heat, but it is not possible at every farm
➢ Boar exposure brings out natural reactions that farmers alone cant reproduce
➢ Nose to nose exposure to a boar will introduce the female to pheromones in the boars saliva, and greatly enhance heat determination
➢ Therefore, the farmer can spray boar releaser pheromone on the sow prior to checking.
What are the pheromonal signalling pathways in mice?
- VNO pathway is sexually dimorphic
- Hormonal cascade from GnRH neurons initiates perinatal testosterone surges in males which masculinizes the pathway.
Signalling in the VNO
• Unlike the main olfactory system, the VNO does not use cyclic nucleotides as second messengers
• VNO cells use members of the transient receptor potential (TRP) superfamily
• rTRP2 is thought to be the main pathway
Effects of TRP2 deletion:
• Rather than display aggression towards each other, males with TRP deletion initiate courtship
• Male aggression to intruder male is eliminated
• Maternal aggression to intruder male is eliminated
→ Aggressio to intruders cruciall depenent on the TRP2 in the VNO
How might the VNO signal behavior?
• VSNs in the TRP2 KO mouse fail to activate in response to pheromones
• Males deficient in TRP2 fail to display aggression to other males
• VNO neurons therefore convey essential sensory information relating to sexual discrimination
• Levels of testosterone are normal, and they still defend themselves if attacked by a resident male
• However, they do not show a fear response to pheromones from other adult males
• The VNO seems likely involved in gender identity
Do humans have a pheromone system?
- VNO system develops in the fetus and is responsible for guiding GnRH neurons
- VNO degenerates before birth
- TRP2 is a pseudogene in humans
- Selective pressure on the TRP2 relaxed at the time of development of old world monkeys when trichromatic vision developed
Evidence for human pheromones:
• Stern & McClintock →odourless compounds from the armpits of women in the late follicular phase of the cycle accelerated the preovulatory surge of LH of recipient women, and shortened their menstrual cycle. Compounds from later in the cycle had the opposite effect – they delayed the LH surge and lengthened cycles
• Tarin and Gomez → males prefer the smell of females in the middle, rather than end of their cycle.
What is the effect of oxytocin knockouts in mice?
• Male mice will attack another male intruder
• Mice exposed to individuals of the opposite sex initially show great interest, but this decreases in successive tests
− normally in the wild-type, the % time spent inspecting the intruder each day does decrease, but if you introduce a new intruder, the time spent inspecting increases back to where it was at the start
− With the oxytocin knockout, the social investigation doesn’t increases when you expose them to a new individual.
→ So oxytocin knockouts have impaired social recognition as they do not seem to recognize new intruders.
− However, oxytocin KO mice get bored just as quickly with the scent as the wildtype, so it has not effected normal sensory capacity.
What are the oxytocin pathways in the brain?
• Synthesised in specialized neurosecretory neurons in the hypothalamus
• These neurons project to the amygdala and also the posterior pituitary gland
• Amygdala is crucial for social recognition
− Destruction of the amygdala blocks fear responses and social recognition
− Administration of oxytocin directly to the amygdala enhancs social recognition in oxytocin gene KO mice
• The amygdala is sexually dimorphic → neurons enlarged by testosterone
What is the behavioural role of oxytocin (and vasopressin) - also in relation to estrogen?
- Vasopressin involved in learning and memory
- Both hormones are involved in social recognition
- Vasopressin often more abundant in the male brain
- Oxytocin equally abundant in both sexes
- Oxytocin plays a role in mice in social recognition in both sexes
Estrogen receptors now known to be crucial in social recognition
• Cells can generate cell specific signaling pathways by signaling through either the alpha or beta estrogen receptor
• Receptor knockouts for both alpha and beta subtypes result in a failure to recognize new intruders.
Summary of receptor knockouts
• KO of either estrogen receptor blocks social recognition
• KO of oxytocin blocks social recognition
• KO of oxytocin receptor blocks social recognition
• In all cases, non-social behaviours and memory unaffected
What is the pathway of olfactory cues, oxytocin and estrogen>
How oxytocin might work:
• Oxytocin neurons projecting from the PVN in the hypothalamus into the amygdala
• Olfactory cues are transported along neurons that project into the amygdala
• Oxytocin modifies the action of neurons in the amygdala to coordinate social recognition
Regulation by estrogen:
• 4 gene ‘micronet network’ comprising ERa, ERb, OT and OTR
• Circulating estrogens affect OT dependent social recognition at two levels:
− Controlling OT production from the PVN through ERb
− Regulating expression of the OTR in the neurons in the amydala via ERa and ERb
- Olfactory signals from the main olfactory bulb and the VNO converge in the amygdala, where OTRs mediate OT gene effects on social recognition
- OT production is regulated by estrogen acting on ERb in the PVN, and response to OT is regulated by estrogen acting through ERa and ERb to modulate expression of the OTR in the neurons in the amygdala
What is the role of oxytocin in human trust?
- Trust pervades in human societies → contributes to economic, political and social success
- Little is known about the biological basis of trust
- Intranasal administration of oxytocin (which plays a key role in social affiliation in non-human mammals) causes a substantial increase in trust among humans, thereby greatly increasing the benefits from social interactions
- Effect is not due to a general increase in the readiness to bear risks → oxytocin specifically affects an individuals willingness to accept social risks arising through interpersonal interactions.
How is the VNO involved in recognition of parasitised individuals?
Female avoidance of parasitized males
• Parasites affect mate choice and mating patterns, with females preferentially selecting parasite free males.
• Choosy females can increase their fitness both directly by reducing their own risk of contagion, and indirectly by enhancing parasite resistance of their offspring
• During mate choice, animals examine urine and faecal cues in an attempt to detect males that are free from disease and parasites.
• Females found the odours of uninfected males more attractive than the odours of infected males
• Females also displayed analgesic responses to the chemical signals of infected males
− Analgesia enables an individual to respond to an anticipated threat
• Females exposed to familiar infected males displayed attenuated analgesia, whereas cues of novel males give heightened analgesia.
Genes and Parasite Recognition
Vasopressin and social behavior:
• Vasopressin is more abundant in male brains than in females, and various studies indicate it is necessary for social recognition apparently, only in males
• However, central administration of a vasopressin receptor antagonist had minimal effects on avoidance of parasitized individuals by male mice
Oxytocin and social recognition
• OT is expressed equally in females and males and is involved in the modulation of social behavior
• Mice deficient in OT showed a deficit in social recognition
• Females with OT knock out impaired in their discrimination of and display of adversive analgesic responses to the urine cues of parasitized males.
