The Role Of Insular Cortex In Mice Observational Fear Learning

Empathy refers to the capacity to understand and respond to the unique affective experiences of another person.It plays an important role in human social cognition and emotional stress and its abnormalities manifest in various psychiatric disorders,such as autism spectrum disorders and schizophrenia.Therefore,studying the neural basis of empathy will not only has important scientific significance in understanding the neural mechanisms of emotional stress,but also provide new idea for the diagnosis and treatment of mental illness due to lack of empathy or disorders.An increasing number of functional neuroimaging investigations suggest that insular cortex(IC)obviously actives in empathy-like behavior.Clinical research showed that IC lesions could impact empathy-like behavior.Besides,the study showed that insular cortex is related to empathy like behavior in mice.However,the mechanism of how insular cortex detects companions’fear and mediates behavioral adaptation is poorly understood.Therefore,this study investigates the role of insular cortex in observational learning behavior in mice and preliminary explores the underlying mechanisms by establishing a mice empathy-like behavior model.1.The model of Observational fear learningFirst,established empathy model-observational fear learning,which was used different paradigms to select the optimal conditions for research such as the way of social defeat and footshock induced observational fear.By comparing two models,it was found that the observation fear learning caused by footshock could stably control the stress intensity received by mice.So,observation fear learning caused by footshock is more stable,and it has been found that mice owned previous experience of an aversive stimulus could induce more robust observational fear.Therefore,it is determined that the observational fear learning model caused by observing the partner received electric shock stimulation will be used for subsequent research.2.Insular cortex participate in observational fear expressionNext,to determine whether IC activity indeed contributed to observational fear expression in mice,we employed one pharmacological approach damaged IC,the result showed the level of observational fear response in mice with lesion was significantly higher.Furthermore,the study employed a pharmacogenetic approach to inactivate and activate neurons in IC during the observational fear learning.The mice inactivated IC showed the level of observational fear was significantly increased during the observational fear learning and the cue context,but there has no effect for the mice activated IC.This result suggested that the insular cortex inhibited in observational fear could enhance the observational fear expression.And immunofluorescence result showed that the number of c-fos positive cells significantly reduced in and the number of PV positive cells obviously increased in insular cortex after mice exposure to the observational fear learning.The is suggested that inhibitory neurons in insular cortex may be involved in the regulatory of observational fear expression.3.Insular cortex participate in observational fear expressionTo further know the underlying mechanism,using a previously established 64-channel multi-electrode array(MED64)recording system to record the change of long-term potentiation(LTP)and long-term depression(LTD)in IC.The result showed that the magnitude of LTD induced after mice underwent observational fear learning was significantly decreased compared with obtained under the control condition and LTP was no changed.Traditionally,LTD is induced by transient Ca2+and requires the activation of NMDA receptors,which initiates a Ca2+influx to trigger a postsynaptic cascade that decreases synaptic efficacy.Therefore,Western Blot was used to detect the expression of related proteins in NMDAR.The results showed that compared with the normal group,NMDAR2B,NMDAR2A and NMDARN1 did not significantly change.This result suggested that observational fear maybe not influence the NMDA expression in IC.4.ConclusionIn summary,this study established an observational fear learning paradigm and found that insular cortex participates in the expression of observational fear in mice.Inactivated IC could alter observational fear expression in mice.Observational fear learning leads to LTD disrupted in IC;imbalance of excitatory and inhibitory neurons regulation in insular cortex may be a potential neural mechanism for empathic behavior.This research provides a new find for empathy fear,and provides new ideas for follow-up drug intervention research.