Non-canonical type 1 cannabinoid receptor signaling regulates night visual processing in the inner rat retina

Sebastián F Estay; Camila Morales-Moraga; Alex H Vielma; Angelina Palacios-Muñoz; Chiayu Q Chiu; Andrés E Chávez

doi:10.1016/j.isci.2024.109920

Non-canonical type 1 cannabinoid receptor signaling regulates night visual processing in the inner rat retina

iScience. 2024 May 7;27(6):109920. doi: 10.1016/j.isci.2024.109920. eCollection 2024 Jun 21.

Authors

Sebastián F Estay^{1

2}, Camila Morales-Moraga², Alex H Vielma², Angelina Palacios-Muñoz², Chiayu Q Chiu², Andrés E Chávez²

Affiliations

¹ Programa de Doctorado en Ciencias, Mención Neurociencia, Valparaíso 2340000, Chile.
² Centro Interdisciplinario de Neurociencia de Valparaíso (CINV), Instituto de Neurociencias, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2340000, Chile.

Abstract

Type 1 cannabinoid receptors (CB1Rs) are expressed in major retinal neurons within the rod-pathway suggesting a role in regulating night visual processing, but the underlying mechanisms remain poorly understood. Using acute rat retinal slices, we show that CB1R activation reduces glutamate release from rod bipolar cell (RBC) axon terminals onto AII and A17 amacrine cells through a pathway that requires exchange proteins directly activated by cAMP (EPAC1/2) signaling. Consequently, CB1R activation abrogates reciprocal GABAergic feedback inhibition from A17 amacrine cells. Moreover, the activation of CB1Rs in vivo enhances and prolongs the time course of the dim-light rod-driven visual responses, an effect that was eliminated when both GABA_A and GABA_C receptors were blocked. Altogether, our findings underscore a non-canonical mechanism by which cannabinoid signaling regulates RBC dyad synapses in the inner retina to regulate dim-light visual responses to fine-tune night vision.

Keywords: Molecular neuroscience; Neuroscience; Sensory neuroscience.