The Role Of Oxytocinergic Neurons In The PVN Region In Regulating Empathy Behavior

1.Background and Purpose :Autism spectrum disorder(ASD)is a neurodevelopmental disorder characterized by repetitive behaviors and social impairments.Empathy refers to the individual’s understanding and experience of other people’s inner emotions and feelings,including the recognition and response to other people’s voices,expressions,physical feelings(such as pain),which has a very important impact on social activities.Recent studies have shown that empathy deficit is one of the core defects and diagnostic criteria for the individuals with autism spectrum disorders,and a large number of studies have shown that improving individual empathy ability is an important treatment to alleviate the abnormal social behavior of autistic patients.At present,the treatment methods based on the improvement of empathy ability are only aimed at the correction of body behavior,and more research is needed on neuromodulation based on molecular or neural circuit.Oxytocin(OT),as a classic neural peptide of prosocial behavior,its effects on empathy need to be systematically studied.With the further understanding of the mechanism of autism,the relationship between empathy deficit and autism is becoming closer.In this study,two types of empathy models were established to observe the different brain regions involved in different empathy behavior paradigms,and on this basis,the role of OT neurons in PVN in fear empathy was studied.2.Methods:2.1 Differences in brain regions regulated by two empathic behavior paradigms: C57B/L mice were used to establish two models of fear emotion empathy and pain transmission empathy,and the success of the models was evaluated by the change of freezing time and the change of pain threshold of mice,respectively.Immunofluorescence histochemical technique was used to observe the expression of cfos in the whole brain,and the numbers of c-fos positive cells in different brain regions were counted.The statistical results showed that different brain regions were involved in the two types of empathy behavior.Effect of oxytocin neurons in PVN on fear empathy behavior.Oxt-cre-/+ transgenic mice were used to establish the CNO-h M3 Dq system by using DREED technology,and the changes of empathy behavior in mice were observed after upregulating the activity of oxytocin neurons in PVN.2.2 The connection between oxytocin neurons and empathic brain areas: Using immunofluorescence double labeling technique,OTR and c-fos staining were performed in the brain areas involved in the regulation of empathy,and the co-labeling was counted to explore whether oxytocin neurons in PVN regulate empathy behavior by acting on empathic brain areas.3.Results:3.1 The difference of brain regions involved in the two types of empathy behavior: In the fear empathy behavior,ACC,PVN,d HPC,LHb,BLA,NAc and v HPC all responded to different degrees,and the cell counts of the above brain regions in the experimental group were significantly different from those in the control group;Different from fear empathy behavior,ACC,BLA,LHb and NAc were involved in pain empathy behavior,but PVN,d HPC and v HPC were not highly responsive to pain empathy.3.2 Oxytocin neurons in PVN positively regulate the level of fear empathy: After exogenous CNO injection,the duration of freezing in CNO group was much longer than that in NS group,that is,the intensity of fear empathy was increased after the activity of oxytocin neurons in PVN was up-regulated.3.3 Oxytocin neurons regulate empathy by acting on empathy brain areas: Immunofluorescence staining results showed that c-fos and OTR expression colocalized in empathy brain areas expressing OTR,which showed that empathy brain areas were regulated by oxytocin,and OT neurons acted on empathy brain area to affect empathy behavior.4.Conclusion:4.1 The nuclei involved in fear empathy and pain empathy are different.ACC,BLA,NAc,PVN,v HPC,d HPC and LHb are involved in fear empathy,while ACC,BLA,LHb and NAc are involved in pain empathy.The involvement of d HPC,v HPC and PVN in pain empathy was not as significant as these in fear empathy.4.2 The oxytocin neurons in the PVN have a positive regulation on empathy behavior,and up-regulating the activity of oxytocin neurons will enhance empathy response.4.3 The oxytocin neurons in the PVN region regulate empathy behavior by acting on the OTR in the empathy participating brain region.