PSYC318-Paper#1

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• Do mice find social interactions to be rewarding?

• Mice tend to avoid rooms that are associated with bad things and tend to return to rooms that are associated with positive things. Does OTR signalling play a role in this?

• Where are the receptors that are mediating this effect?    

• Is oxytocin released in the NAc?    

•  Do these PVN neurons project to the NAc AND make oxytocin?

• Which neurons in the NAc have oxytocin receptors?    

• Are the OTRs on these cells actually mediating this effect?

• Does OT released in the NAc affect the physiology of cells?

• Do any neurons that project to the NAc from anywhere else in the brain have OTRs on them, affecting the probability of other neurotransmitter (glutamate) release in the NAc?    

• + PP for social interactions

• CPP

• question

• method

• conclusion

• Inject an OTR antagonist  intraparetoneal    

• globally blocking OTR eliminates social interactions   

• infusion OTR antagonist w/ fluorescent dye  NAc on either side

• abolished CPP   

• Gene therapy w/ RbV retrograde, NAc synapses glow, brain slices

• some hypothalamus neurons that project to the NAc make oxytocin    

• (PVN) of the hypothalamus projects to the NAc 

• antibody binds to OXT & glows (retrograde)

• cells project to NAc glow

• red neurones make OXT peptide & yellowish NAc project & make OXT.    

• PVN makes OXT and NAc releases

• ·      Only some glial cells and one type of GABAergic interneuron express OTRs in the NAc

• conditional oxytocin receptor knockout mouse + virus

• AAV, GFP   

• ·      OTR gene deleted NAc cells

• record the electrical activity of NAc projection neurons + OXT

• decreasing the amount of glutamate release onto these projection neurons    

• RbV,  cells that project to the NAc glow red    

• conditional OTR knockout mouse    

• no longer a conditioned place preference    

• Do the OTRs on axon terminals that project to the NAc affect social reward?    

• conditional OTR knockout +  RbV    

• neurons projecting to NAc will loose their ability to make OTR 

• No social reward preference

• conditional OTR knockout mouse + AAV    

• systematically checking cell types and deleting the ability of each cell type to make OTR    

• lacking OTR just in the dorsal raphe don’t have a social reward place preference    

• Which dorsal raphe neurons are needed for this effect?    

• OTR reporter mous    

• label cells that project to the NAc w/ RbV-TdTomato    

• immunohistochemistry to stain for enzyme make serotonin 

• all cells w/serotonin (5-HT) receptor glow blue    

• Apply a serotonin receptor agonist, to NAc cell    

• stimulate nearby axons and find that serotonin causes less glutamate release from those axons

• Further application of OT does nothing 

• OT is affecting serotonin release which affects glutamate release    

• Blocking serotonin w/ receptor antagonist    

• blocks social reward place preference

• Removing OTR just from serotonin neurons 

• conditional OTR knockout mouse    

• deliver Cre and GFP to dorsal raphe neurons no OTR

• OT does not change the strength of the glutamatergic connections