Abstract
Purpose :
Amacrine cells (ACs) are the least understood cell class in the retina due to the lack of genetic access and limited accessibility for patch-clamp recording. In this study, we combined mouse genetics, genetic profiling, functional imaging, and electrophysiology recording to discover new AC types and analyze their functional properties.
Methods :
We use Cre/tTA intersectional genetics to identify new AC types, followed by analyzing their genetic profiles with single cell RNA sequencing (scRNA-seq), and then characterize their functional properties and circuit roles with GCaMP and iGluSnFr imaging, combined with electrophysiology recording.
Results :
With Slc32a1-iCreER/Scg2-tTA intersectional strategy, we identified a new narrow-field AC subtype in the mouse retina, named Scg2-AC2. To our surprise, Scg2-AC2 showed light responses unexpected from morphological features. Scg2-AC2 stratified in the ON layer, but was activated by light decrement (OFF) in the surround and inhibited by light increment (ON) in the center. The ON center inhibition was created by sign-inverting mGluR8 activated by glutamate released from ON bipolar cells. The OFF surround activation was mediated by a wide-filed AC that received excitation from sustained OFF bipolar cells in the OFF sublamina and then made gap junction connections with Scg2-AC2 and activated it in the dark.
Conclusions :
This study discovered a new AC type inhibited by bipolar cells via glutamate transmission. The structure and function correlation of Scg2-AC2 positions its potential role in “crossover inhibition” between ON and OFF channels by carrying OFF inhibition to the ON channel to enhance light sensitivity of RGCs in the dark.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.