PSYC318-Paper#1

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