| Human and most mammals develop various kinds of social bonds inthe different stages throughout the whole life history,such as parent-infant bond,sibling bond,pair bond and so on.These stable and positive social bonds play an important role in their physical health,mental development and well-being.At the same time,these bonds can also reduce the individual's sensitivity to stress and the risk of suffering from anxiety,depression and other emotional disorders.If the stable social bondsare disturbed,it may cause many negative effects.Previous animal studies have shown that:the disruption of social bonds(such as maternal separation,paternal deprivation,cross-fostering,social isolation,etc.)can affect individual emotion and behavior,and these processes are regulated by specific neural mechanisms.For adults,pair bond is one of the most important social bonds.In recent years,with the rapid development of economy,social change and the change of people's concept of love and marriage,the divorce rate is rising,and the related mental diseases are also increasing year by yearin human society.Therefore,it is necessary to establish animal models to simulate the special phenomena of separation,divorce or widowed in human,to study the internal mechanism of the influence of pair bond interferences on emotion and behavior.In the mating system of animals,monogamous animals show two main behavioral phenotypes:selective attachment to their pair(monogamy)and paternal involvement in pupscaring.However,only 3%-5%of mammal species are monogamous,which seriously restricts the study of pair bond.In addition,most of the existing studies on monogamous rodents(such as prairie vole,California mouse,etc.)to study pair bond formation,maintenance and related neuromechanisms,while the research on pair bond interferences(such as pair bondinterruption)is relatively less.Researches on unstable pair bond mostly focus on males,while females are often ignored by researchers because of their complex reproductive cycle.So,compared with the male,does the effect of unstable pair bond have the same effect on the female?What is its neuromechanisms?None of these questions is clear.Oxytocin(OT)is the key factor to regulate social bonds,and also participates in the regulation of emotions.Many studies have shown that exogenous injection of OT can reduce anxiety-like behavior in prairie voles,rats and mice.In addition,the increase of OT level in brain can promote the establishment of social bonds.The disruption of social bonds such as social isolation,maternal separation,and paternal deprivation will damage OT system,and then have a negative impact on the physiology,emotion,and behavior.Therefore,the change of OT system activity may be the potential neuromechanisms of emotional and behavioral changes caused by unstable pair bond.Social identification is the necessary premise of social recognition,which is one kind of complex social behavior that can identify the same species of familiar or unfamiliar individuals,and is the effective basis for all kinds of social behavior.The formation of social bonds and the construction of social structure are based on social recognition.Nowadays,whether there is recognition dysfunction has become one of the most important factorsin diagnosing the psychiatric disorders.Previous studies mostly focus on spatial recognition,learning and memory.However,l ittle is known about social recognition.In addition,most studies focus on the study of emotion,but little is known about whether the stress will affect the social recognition ability of animals and the related neuromechanisms.Therefore,in this study,we want to further explore pair bond interruption could impair the social recognition ability of adult mandarin voles and its potential neuromechanisms.Mandarin voles(Microtus mandarinus)arethe high sociality rodent.Therefore,the study selected female mandarin voles as the research object to supplement the previous studies of female mandarin voles.Through the study of the influence of pair bond interruption on female emotion,behavior and its neuromechanisms,we can clarify the influence of unstable pair bond on females and its regulatory mechanism.In this experiment,virgin female voles were induced to be in the estrus stage by exposing to the nesting material of unrelated male.And then,females were cohabitated with an unfamiliar adult male vole.After 5 days of cohabitation,all paired females were randomly divided into two groups:control group(animals were continuously stayed with their partner,even during the subsequent behavior tests),and interruption group(animals were separated from their partner and raised alone in one cage).Two weeks of modeling was followed by the social recognition test.After behavior test,animals were anesthetized and their brains were collected for immunofluorescence and Western Blot.The immunofluorescence was used to explore the expression of OT and Fos immunoreactive neurons(OT-irand Fos-ir)in paraventricular nucleus(PVN).Western blot was used to measure the level of OTR protein in Nucleus Accumbens Shell(NAcSh).In NAcSh,OT or OTR antagonists(OTA)were microinjected to verify whether OT system was involved in the social recognition changes induced by pair bond interruption.In addition,chemical genetics method was used to verify whether the OT neurons projection from PVN to NAcSh played an indispensable role in the social recognition changes induced by pair bond interruption.The experimental results are shown as follows:1.Pair bond interruption impairs the social recognition ability of female mandarin volesThe social recognition ability of voles was tested by habituation/dishabituation paradigm.In the control group,there was significant difference between the fourth stage and the first stage,the fourth stage and the fifth stage and there was no significant difference between the fourth stage and the fifth stage.And there had no significant difference in the three stages of the interruption group.In addition,the social recognition index in the control group was significantly higher than zero,and significantly higher than the interruption group.The fatigue index between control group and interruption group hadno significant difference.These results suggested that pair bond interruption can impair the social recognition ability in female voles.2.Pair bond interruption reduces the number of active OT neurons in PVN of female mandarin volesUsing immunofluorescence test to research the expression of OT-ir and Fos-ir neurons in PVN.The results showed that there was no significant difference in thenumber of OT-ir neurons between the control group and the interruption group.The number of Fos-ir neurons and OT neurons expressing c-Fos in interruption group were significantly lower than control group.These results suggested that the expression of Fos-ir neurons in PVN can be significantly reduced by pair bond interruption.3.Pair bond interruption reduces the level of OTR in NAcSh of female mandarin volesThe relative expression of OTR protein in NAcSh was examined by Western blot test.The results showed that the relative density of OTR protein in NAcSh of the interruption group was significantly lower than control group.These results suggested that pair bond interruption can significantly reduce the level of OTR in NAcSh of female mandarin voles.4.Effects of exogenous injection of OT/OTA on the social recognition ability of female mandarin volesThrough pharmacological methods,OT or OTA was injected into NAcSh to detect whether OT system was involved in the social recognition changes induced by pair bond interruption.These results showed that the control group after injection of lOng or 100ng OTA could simulate the social recognitive impairment induced by the pair bond interruption.The interruption group could reverse the social recognition impairment induced by the interruption group after injection of 1Ong OT.In the interruption group,the social recognitive ability was impaired after injection with 10ng OT and 10ng OTA.These results revealed that the combination of OT and OTR at NAcSh is one of the main regulatory mechanisms of social recognitive impairment induced by pair bond interruption.5.Specific manipulation of OT system in PVN-NAcShneural circuit can regulate social recognition ability of female mandarin volesUsing chemical genetics to investigate the regulatory role of OT system in PVN-NAcSh neural circuit in social recognition ability changes induced by pair bond interruption.The results showed that the interruption group voles were in traperitoneally injected with CNO to activate the OT neuron projection from PVN to NAcSh,which couldrestore the social recognition ability.However,in the control group,the voles were intraperitoneally injected with CNO to inhibit the OT neuron projection from PVN to NAcSh,which could impair the social recognition ability.These results implied that targeted activation of OT system in PVN-NAcSh neural circuit can restore social recognition ability.And,targeted inhibition of OT system in PVN-NAcSh neural circuit can simulate social recognition impairment induced by pair bond interruption.In conclusion,the pair bond interruption could impair the social recognition ability,significantly reduced the expression of OT-imeurons in PVN,and significantly reduced the level of OTR in NAcSh of female mandarin voles.Exogenous injection of OT in NAcSh or targeted activation of OT neuron projection from PVN to NAcSh could restore the social recognition ability impairment induced by pair bond interruption.In addition,exogenous injection of OTA in NAcSh or targeted inhibition the OT neuron projection from PVN to NAcSh could simulate the social recognition impairment induced by pair bond interruption.These results suggested that the social recognition ability changes induced bypair bond interruption in female mandarin voles was regulated by the activity of OT system in PVN-NAcSh neural circuit. |
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