PT  - JOURNAL ARTICLE
AU  - Franklin S. Caval-Holme
AU  - Marcos L. Aranda
AU  - Andy Quaen Chen
AU  - Alexandre Tiriac
AU  - Yizhen Zhang
AU  - Benjamin Smith
AU  - Lutz Birnbaumer
AU  - Tiffany M. Schmidt
AU  - Marla B. Feller
TI  - The Retinal Basis of Light Aversion in Neonatal Mice
AID  - 10.1101/2022.01.20.477130
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.01.20.477130
4099  - http://biorxiv.org/content/early/2022/01/22/2022.01.20.477130.short
4100  - http://biorxiv.org/content/early/2022/01/22/2022.01.20.477130.full
AB  - Aversive responses to bright light (photoaversion) require signaling from the eye to the brain. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) encode absolute light intensity and are thought to provide the light signals for photoaversion. Consistent with this, neonatal mice exhibit photoaversion prior to the developmental onset of image vision, and melanopsin deletion abolishes photoaversion in neonates. It is not well understood how the population of ipRGCs, which constitutes multiple physiologically distinct types (denoted M1-M6 in mouse) encodes light stimuli to produce an aversive response. Here, we provide several lines of evidence that M1 ipRGCs that lack the Brn3b transcription factor drive photoaversion in neonatal mice. First, neonatal mice lacking TRPC6 and TRPC7 ion channels failed to turn away from bright light, while two photon Ca2+ imaging of their acutely isolated retinas revealed reduced photosensitivity in M1 ipRGCs, but not other ipRGC types. Second, mice in which all ipRGC types except for Brn3b-negative M1 ipRGCs are ablated, exhibited normal photoaversion. Third, pharmacological blockade or genetic knockout of gap junction channels expressed by ipRGCs, which reduces the light sensitivity of M2-M6 ipRGCs in the neonatal retina, had small effects on photoaversion only at the brightest light intensities. Finally, M1s were not strongly depolarized by spontaneous retinal waves, a robust source of activity in the developing retina that depolarizes all other ipRGC types. M1s therefore constitute a separate information channel between the neonatal retina and brain that could ensure behavioral responses to light but not spontaneous retinal waves.Competing Interest StatementThe authors have declared no competing interest.