Neural Mechanism Of Anterior Cingulate Cortex Regulating Visually-evoked Innate Fear Behavior

The neural mechanisms involved in processing fear information are complex and involve complex co-regulation of multiple brain regions.Among these,the cortex plays an important role in the integration of fear information and in the regulation of behavior.So far,most research has focused on the mechanisms by which subcortical nuclei regulate innate fear,and it is unclear whether the cortex is involved in the regulation of subcortical neural circuits associated with innate fear and the mechanisms by which it is regulated.The Anterior Cingulate Cortex(ACC)plays a key role in the regulation of many fear behaviors and has been widely reported to be involved in the regulation of learned fear,but there is no evidence to suggest whether the ACC is involved in the regulation of visually-evoked innate fear.The top-down regulation of innate fear by higher cortical brain regions such as the ACC is also a more critical part of how we understand fear processing mechanisms.Therefore,we focused on"the neural mechanisms involved in the regulation of visually-evoked innate fear by ACC"and explored the neuronal types and downstream neural pathways involved in this process.In addition,since abnormalities in emotion processing can lead to abnormalities in fear response and anxiety levels,this study also initially explored the effects and mechanisms of ACC on the regulation of anxiety states.We use animal behavior tests combined with immediate early activity-dependent protein c-Fos labeling,immunofluorescence staining,fiber photometry,optogenetics,chemical genetics and other technical means to explore the neural mechanism of ACC involved in the regulation of visually-evoked innate fear behavior,based on the classical Looming stimulus paradigm.It was preliminarily confirmed that ACC CaMK??~+neurons are involved in regulating visually-evoked innate defensive behavior,and activation of excitatory projections from ACC to the anterior part of lateral posterior nucleus(LPa)rather than the Superior Colliculus(SC)decrease visually-evoked innate fear behavior.Furthermore,we found that activation of those two projection pathways,ACC CaMK??~+neurons projecting to Lpa and SC,both produce anxiolytic effects.It is suggested that ACC CaMK??~+neurons are involved in regulating anxiety levels.Analyzing the mechanisms that regulate the innate fear response of higher cortical layers,including the ACC,to the threat of natural enemies is an important part of constructing the neuroregulatory network of innate fear and understanding the mechanisms of fear information processing.In this study,we preliminarily resolved the neural circuit mechanisms involved in the regulation of visual innate fear by ACC,and confirmed that the activation of excitatory projections from ACC to LPa is involved in regulating the visually-evoked innate defensive behavior.This study deepens our understanding of the involvement of cortical areas in the regulation of visual innate fear and provides an experimental basis for further analysis and construction of the neural network structure of visually-evoked innate fear.