A Retinoraphe Projection Regulates Serotonergic Activity And Looming-evoked Defensive Behaviour

Defensive behavior in response to rapidly approaching objects indicating threats is an innate response remarkably conserved across species,including humans.Recent research found that rapidly approaching objects(looming stimulation)could induce flight or freezing responses in mice,which is believed to be regulated by subcortical visual pathways.However,the neural circuits that begin in the retina that mediate this behavior remain imcompletely understood.In this study,the structure and function of looming related visual circuits were studied by comibing an array of state-of-the-art brain circuit interrogation tools,including transneuronal virus tracing,optogenetics,chemogenetics,fibre photometry,eletrophysiolgy,and behaviroral tests.We identified a subset of retinal ganglion cells(RGCs)that controls mouse looming-evoked defensive responses through axonal collaterals to the dorsal raphe nuclei(DRN)and superior colliculus(SC).On one hand,looming stimulation could initate defensive behavior through activating SC-lateral posterior nuclei(LP)-amygdala(Am)pathway.On the other hand,looming signals transmitted by RGCs could result in the inhibition of DRN serotonergic system via direct activation of DRN GABA neurons,which appears to be required to facilitate looming-evoked defensive responses.To our knowledge,this study is the first to investigate the morphological and physiological features of looming-sensitive RGCs.The looming-evoked visual circuits described in this study expands the impacts of light on mood-related behaviors,and provide important mechanism for the diagnosis and treatment of fear related disorders,such as autism and phobia.