Effects Of Paternal Deprivation On Empathy Levels And Mechanisms Involved In The Oxytocin System

Empathy refers to the ability to empathize with the emotions and mental states of others and to respond in some way.Research has shown that empathy is not only found in primates,but also in animals such as birds and rodents.Normal empathy is of great significance to the harmonious relationship between people and the construction of a harmonious and stable society.On the other hand,the injury of empathy may lead to selfishness,which leads to indifference and disharmony between people,social violence,and slow social development.Moreover,the occurrence of some diseases such as depression and autism are also closely related to the impairment of empathy.Therefore,the study on the mechanism underlying empathy can promote people's understanding of the occurrence mechanism of empathy,and is of great significance for the harmonious and stable development of society and the prevention and treatment of related mental diseases.Functionally,empathy can be divided into emotional empathy and cognitive empathy,and cognitive empathy is a higher level than emotional empathy.Emotional empathy refers to the understanding of other people's emotional states,that is,I feel what you feel,for example,in response to a baby crying.Cognitive empathy can not only feel the emotions of others,but also further predict the motivation of others' future behavior.Emotional empathy and cognitive empathy are independent of each other and related to each other.In recent years,people have gradually realized the importance of empathy and have made preliminary research on empathy,but the research on the mechanism of empathy and the neural circuit of empathy is not very clear.Parental care plays an important role in the survival and development of individuals.The mother usually plays the most important or only role in rearing the offspring,therefore,most of the studies mainly focus on effects of maternal parental isolation or maternal deprivation,but there are few studies on the influence of paternal deprivation.Numerous social reports have shown that children who lack paternal education in childhood are more prone to alcoholism and crime,and some studies have shown that parenthood can affect aggressive behavior and related neuromaterial development in California mice.So paternal parents also play a crucial role in the development of their offspring.Whether the absence of a paternal affects the normal development of the offspring,leading to changes in their level of empathy,is unknown.Therefore,this study selected the monogamous mandarin voles with high sociality as the research object to explore whether paternal deprivation has effects on the level of empathy and the mechanism of neuroendocrine parameters in mandarin voles.Studies have shown that male mandarin voles have high levels of paternal behavior,which is an ideal animal model to study the effect of paternal deprivation on offspring behavior.First of all,after birth of offspring,fathers were removed from breeding cages.After the offspring were in adulthood,their levels of anxiety-like behaviors in open fields,scolibity(social approach to avoidance test),emotional empathy(pain empathy test,cognitive empathy experiment(consolation test),and the OT(oxytocin)neuron activity(OT and c-Fos expression)in the PVN(paraventricular nucleus)brain regions and OTR levels(oxytocin receptor mRNA level ACC were investigated.At the same time,we injected OTR interference virus in the ACC brain region of normal mandarin voles and OTR overexpression virus into the ACC brain region of offspring with patern deprivation to further verify the influence of OTR level on social behavior and empathy level.Finally,we validated the role of the PVN-ACC neural circuit in regulating empathy using chemogenetics.Experimental results are as follows:1.The influence of paternal deprivation on behaviorThe results of open field experiment showed that paternal deprivation decreased the percentage of time in the central area of open field in normal female and male mandarin voles,but had no effect on the total distance of open field traveled.Social approach avoidance experiments showed that paternal deprivation reduced the behavior of normal female and male mandarin voles in approaching strangers of the same species.The pain empathy test using observing mandarin voles with foot formaldehyde injection showed that male parental deprivation decreased the time of Paw-licking(licking),Gnawing(biting the paddle),and Interesting(head-toward to the Demostrator)behavior of normal female and male mandarin voles,and increased the time of Neglecting(head-not toward to the Demostrator)behavior.There was no effect on Self-grooming or Circling time.Pain empathy experiments showed that paternal deprivation reduced the allogrooming behavior of normal female and male mandarin voles to their startled companions with foot shock.2.Effects of paternal deprivation on OT neuron activity(co-expression of OT and c-Fos)in the PVN and the level of male and female mandarin voles OTR in ACCPaternal deprivation resulted in decreased OT neuron activity(co-expression of OT and c-Fos)in the PVN of male and female mandarin voles and decreased OTR mRNA levels in ACC brain regions.3.The influence of OTR overexpression and interfering on behaviorIn the open field experiment,compared with the control group,the percentage of time in the central area in male mandarin voles injected with OTR overexpressing virus increased significantly in the experimental group,but this effect was not found in the female.In both females and males,the total distance of open field movement had no effect.The social approach and avoidance experiment showed that the interaction rate between female mandarin voles and strange conspecific individuals was increased by the injection of OTR overexpression virus,but there was no significant difference between male and female mandarin voles.The pain empathy test showed that compared with the control group,the Paw-licking time of female voles in the experimental group injected with OTR overexpression virus increased,while duration of the Gnawing,Interesting and Circling behavior time of female and male voles in the experimental group increased,and the Neglecting behavior time of female and male voles decreased.The consolation test showed that female and male mandarin voles in the OTR overexpressing group spent longer time in allogrooming their partners than those in the control group.The open field experiment showed that percentage of time in the central area in female and male mandarin voles in the experimental group injected with OTR interference virus decreased significantly compared with the control group.Social approach and avoidance experiments showed that the interaction rate between male and female mandarin voles and strangers was decreased by the injection of OTR interference virus.The pain empathy test showed that compared with the control group,the time of Paw-licking,Gnawing and Interesting behavior of female and male mandarin voles injected with the OTR interference virus increased,while the time of Neglecting behavior increased.The consolation test showed that female and male mandarin voles injected with the OTR interference virus showed a reduced time of consoling behavior to their startled companions compared with the control group.4.Effects of chemogenetic manipulation of PVN-ACC OT neuron projections on behaviorsPain empathy test showed that injection of saline or CNO produced no effects on Paw-licking,Gnawing,Interesting,Circling and Neglecting behaviors between female and male mandarin voles in the control virus group.Chemogenetic inhibition of PVN-ACC OT neuron projections reduced Paw-licking.Similarly,in the fear transfer experiment,injection of saline or CNO produced no effects on Paw-licking,Gnawing,Interesting,Circling and Neglecting behaviors between female and male mandarin voles in the control virus group.Chemogenetic inhibition of PVN-ACC OT neuron projections reduced allogrooming behavior to voles with foot shock.Pain empathy experiment showed that injection of CNO did not affect Paw-licking,Gnawing,Interesting,Circling and Neglecting behaviors between female and male mandarin voles in control virus group.Chemogenetic activation of PVN-ACC OT neuron projections increased the time of Paw-licking,Circling,Gnawing,and Interesting behavior increased,while reduced Neglecting behavior In the fear transfer experiment,injection of CNO did not affect allogrooming behavior in control virus group.Chemogenetic activation of PVN-ACC OT neuron projections increased allogrooming behavior.This result shows that PVN-ACC OT neuron projections are involved in regulation of empathy behaviors.In conclusion,we concluded that the reason why paternal deprivation leads to these behavioral changes may be that paternal deprivation leads to a decrease in the number of OT neurons that PVN projects to ACC and a decrease in the level of OTR.This study reveals the neuroendocrine mechanism by which paternal deprivation affects empathy in highly social mandarin voles,and helps us to understand the mechanism by which paternal deprivation induces emotional and empathic disorders,and provides some new ideas for the prevention and treatment of psychiatric disorders related to empathic disorders.