Cell Type-specific Endocannabinoid System In Superior Colliculus Modulates Visual Innate Fear Behavior

Innate fear behaviors are defensive responses to specific,potentially life-threatening stimuli,which are both essential for maintaining individual survival and the reproduction of species.However,negative emotions,such as anxiety and depression,and even psychiatric disorders are possibly evoked when encountering threaten stimuli of long standing.Therefore,to sophisticatedly characterizate the movement features of innate fear behavior and to analyze the structure and function of its neural circuit,is important for learnning the modulatory mechanism of innate fear and understanding the pathogenesis of abnormal fear response relaitve mental disorders.This study is focus on evolutionarily conserved visually-evoked innate fear behavior.Superior colliculus(SC),a subcortical nucleus,is critical for processing visual innate fear information whereby cell-type-specific neural circuits integrate and transmit visual threat signals to trigger defensive behavioral responses to fear signaling.The neurotransmitters/neuromodulators are highly involved in this process.Our group has found that the cannabinoid receptor 1(CB₁R)of SC GABAergic neurons are participate in modulating innate fear reponse.However,the subcellular types and the projection characteristics of GABAergic neurons involved in the regulation of visual innate fear in SC,as well as sex differential regulation mechanism of CB₁R remain to be further elucidated.In summary,this study combined a high-precision 3D animal motion-capture and analysis system,immunohistochemistry,in situ hybridization,cell-type-specific neural circuit tracing and CB₁R gene knockdown technique to(1)resolve the fine features of spontaneous movements in mice and develop a 3D animal motion-capture and analysis system applicable to the paradigm of visually-evoked innate fear behavior,and(2)map the distribution and projection of GABAergic subtypes of neurons in the SC and(3)investigate the role of CB₁Rs in the regulation of different subtypes of GABAergic neurons in visually-evoked innate fear behavior.The findings revealed:(1)that both sexes showed diurnal differences in spontaneous behavior,with more exploratory-like behavior during the day and more grooming-like behavior at night;(2)the device we built to accurately investigate visully-evoked defensive behavior was able to restore the dynamic action of this process;(3)PV-positive cells in the SC are co-labeled with CB₁Rs,and(4)knockdown the CB₁R expression in SC PV⁺-GABAergic neurons enhanced looming-evoked defensive behavior in male mice.There results provided stable supports for understanding the neural modulatory mechanisms of visully-evoked innate fear response.