Manipulating Fear Extinction Via Optogenetic Modulation Of Ectorhinal Cortex Glutamatergic Inputs To Infralimbic Prefrontal Cortex

Negative emotions such as fear and anxiety are a kind of highly conservative and adaptive response of the body to the environment,which will have a profound impact on our attention,cognition,decision-making and various conscious behaviors.Failure to properly regulate negative emotions increases the risk of various mental illnesses,including depression and post-traumatic stress disorder.It is necessary to deeply explore the physiological mechanism behind emotional disorders for clinical development of new effective treatments.Conditioned fear extinction provides an excellent model for examining how emotional dysfuction-induced changes in brain structure and function are related to emotional dysfuction-induced changes in behavior.According to its different functions,Medial temporal lobe(MTL)can be roughly divided into the following subregions: the hippocampal?parahippocampal?perirhinal(PRh),entorhinal(Ent)and ectorhinal(Ect)cortices.Many existing studies have focused on the role of regions such as hippocampal and entorhinal cortex in learning,memory,and emotional regulation.However,owing to the close connection between Ect and PRh,in the past Ect was viewed as a part of PRh,and there was no specific research about the function of Ect.In recent years,more detailed anatomical researches have shown that Ect has a specific physiological structure,but for now,our understanding of the structure and function of Ect is still limited.In this article,we focus on the role of Ect in regulating extinction of fear memory.In this paper,we mainly use optogenetic technology to regulate the downstream projection of Ect.By observing the behavioral responses of mice in experiment of conditioned fear extinction,we explore the role of Ect in regulating fear extinction.We found that the glutamatergic neurocircuit from Ect project to IL could bidirectional manipulate of fear extinction.As a result,an important new neural circuit related to learning,memory,and emotional regulation has been discovered.