The Role Of Two Interneurons Types Within ACC In Mice Observational Fear Learning

Empathy is an evolutionary preserved ability necessary for the survival of animal groups,and rodents' s behavior in observational fear test reflect their ability to engender emotional empathy.Anterior cingulate cortex(ACC)is assumed to play a central role in empathy in humans,primates or rodents.ACC interneurons,especially perisomatically targeting parvalbumin(PV)and dendritically targeting somatostain(SOM)interneurons,are endowed with cognitive and emotional functions.However,the role of these two neuronal types within the ACC in mediating empathy is poorly understood.By using DREADD system in rodent to inactivate ACC,we confirmed ACC is necessary in regulating freezing response during observational fear test.Then we also expressed the excitatory h M3 Q designer receptor exclusively activated by a designer drug(DREADD)in cre-expressing mouse lines to selectively activate ACC PV or SOM interneurons of observer mice after treated with clozapine-N-oxide(CNO;3 mg/kg,i.p.)before observational fear test.We found that DREADD exication of PV interneurons significantly reduced observer mice's freezing time when observing cagemate receiving footshock,whereas activation of SOM interneurons scarcely showed effect on observer's freezing response.We conjectured that different upstream inputs to these two interneuron types might contribute to their different perfermances in observatioanl fear test,so we used RV monosynaptic retrograde tracing to find the inputs afferent to PV or SOM interneurons respectively.We found that both of them receive inputs from Hippoc,MD,AV/AM,CI,DB,but the number of AV/AM projection to PV was significant than SOM,however DB was in the opposite,and there were also sparse afferent from VM,MS targetting ACC PV,and LH,Fr A,LO/MO/VO targetting SOM,so it was possible that different inputs to ACC PV or SOM interneurons would explain their different roles in OFT.Our results provided direct evidence of the ro le of ACC PV interneurons in regulating rodent emotional empathy.It will allow detailed analysis of neurocircuit underlying rodent empathy and provide evidence for PV interneurons as therapeutic targets for neuropsychiatric disorders with abnormal empathy like autism in the future.