A Non-canonical Excitatory PV RGC-PV SC Visual Pathway for Mediating the Looming-evoked Innate Defensive Response

Parvalbumin-positive retinal ganglion cells (PV+ RGCs) are an essential subset of RGCs found in various species. However, their role in transmitting visual information remains unclear. Here, we characterized PV+ RGCs in the retina and explored the functions of the PV+ RGC-mediated visual pathway. By applying multiple viral tracing strategies, we investigated the downstream of PV+ RGCs across the whole brain. Interestingly, we found that the PV+ RGCs provided direct monosynaptic input to PV+ excitatory neurons in the superficial layers of the superior colliculus (SC). Ablation or suppression of SC-projecting PV+ RGCs abolished or severely impaired the flight response to looming visual stimuli in mice without affecting visual acuity. Furthermore, using transcriptome expression profiling of individual cells and immunofluorescence colocalization for RGCs, we found that PV+ RGCs are predominant glutamatergic neurons. Thus, our findings indicate the critical role of PV+ RGCs in an innate defensive response and suggest a non-canonical subcortical visual pathway from excitatory PV+ RGCs to PV+ SC neurons that regulates looming visual stimuli. These results provide a potential target for intervening and treating diseases related to this circuit, such as schizophrenia and autism.