GABAergic Retinal Ganglion Cells Projecting to the Superior Colliculus Mediate the Looming-Evoked Flight Response
Man Yuan1 · Gao Tan1 · Danrui Cai1 · Xue Luo1 · Kejiong Shen1 · Qinqin Deng1 · Xinlan Lei1 · Wen‑Bo Zeng2 · Min‑Hua Luo2 · Lu Huang3,4 · Chaoran Ren4,5 · Yin Shen1,61 Eye Center, Renmin Hospital of Wuhan University, Wuhan University, Wuhan 430060, Hubei, China
2 State Key Laboratory of Virology, CAS Center for Excellence in Brain Science and Intelligence Technology, Wuhan Institute of Virology, Wuhan 430071, China
3 Department of Neurology and Stroke Center, The First Afliated Hospital of Jinan University, Guangzhou 510632, China
4 Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou 510632, China
5 Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510530, China
6 Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan 430071, China
Abstract
The looming stimulus-evoked flight response to approaching predators is a defensive behavior in most animals. However, how looming stimuli are detected in the retina and transmitted to the brain remains unclear. Here, we report that a group of GABAergic retinal ganglion cells (RGCs) projecting to the superior colliculus (SC) transmit looming signals from the retina to the brain, mediating the looming-evoked flight behavior by releasing GABA. GAD2-Cre and vGAT-Cre transgenic mice were used in combination with Cre-activated anterograde or retrograde tracer viruses to map the inputs to specific GABAergic RGC circuits. Optogenetic technology was used to assess the function of SC-projecting GABAergic RGCs (scpgRGCs) in the SC. FDIO-DTA (Flp-dependent Double-Floxed Inverted Open reading frame-Diphtheria toxin) combined with the FLP (Florfenicol, Lincomycin & Prednisolone) approach was used to ablate or silence scpgRGCs. In the mouse retina, GABAergic RGCs project to different brain areas, including the SC. ScpgRGCs are monosynaptically connected to parvalbumin-positive SC neurons known to be required for the looming-evoked flight response. Optogenetic activation of scpgRGCs triggers GABA-mediated inhibition in SC neurons. Ablation or silencing of scpgRGCs compromises looming-evoked flight responses without affecting image-forming functions. Our study reveals that scpgRGCs control the looming-evoked flight response by regulating SC neurons via GABA, providing novel insight into the regulation of innate defensive behaviors.
Keywords
scpgRGCs; Innate defensive behavior; GABA; Looming; Superior colliculus; Flight response
