A Non-canonical Excitatory PV RGC–PV SC Visual Pathway for Mediating the Looming-evoked Innate Defensive Response
Man Yuan1 · Sen Jin2,4 · Gao Tan1 · Siyuan Song3 · Yizong Liu1 · Huadong Wang2,4 · Yin Shen1,51 Eye Center, Renmin Hospital of Wuhan University, Wuhan University, Wuhan 430060, China
2 The Brain Cognition and Brain Disease Institute, Shenzhen Key Laboratory of Viral Vectors for Biomedicine, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences (CAS), Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, National Medical Products Administration Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal Products, Shenzhen Key Laboratory of Quality Control Technology for Virus-Based Therapeutics, Guangdong Provincial Medical Products Administration, Shenzhen 518055, China
3 Jan and Dan Duncan Neurological Research Institute, Baylor College of Medicine, Houston 77030, USA
4 State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Key Laboratory of Magnetic Resonance in Biological Systems, Wuhan Center for Magnetic Resonance, Innovation Academy for Precision Measurement Science and Technology, CAS, Wuhan 430071, China
5 Frontier Science Center of Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan 430071, China
Abstract
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.
Keywords
Parvalbumin-positive retinal ganglion cell; Innate fear; Superior colliculus; Excitatory-excitatory neuronal connection; Looming-evoked defensive response; Subcortical pathway
