Connectomic analysis reveals an interneuron with an integral role in the retinal circuit for night vision.

Silvia Jh Park,Joshua H Singer,Kevin L Briggman,Jonathan B Demb,Hae-Lim Lee,Na Young Jun,Jiang-Bin Ke,Padideh Ghorbani,Pouyan Rahmani,Nao Rho,Evan E Lieberman,In-Jung Kim

doi:10.7554/elife.56077

Abstract

Night vision in mammals depends fundamentally on rod photoreceptors and the well-studied rod bipolar (RB) cell pathway. The central neuron in this pathway, the AII amacrine cell (AC), exhibits a spatially tuned receptive field, composed of an excitatory center and an inhibitory surround, that propagates to ganglion cells, the retina's projection neurons. The circuitry underlying the surround of the AII, however, remains unresolved. Here, we combined structural, functional and optogenetic analyses of the mouse retina to discover that surround inhibition of the AII depends primarily on a single interneuron type, the NOS-1 AC: a multistratified, axon-bearing GABAergic cell, with dendrites in both ON and OFF synaptic layers, but with a pure ON (depolarizing) response to light. Our study demonstrates generally that novel neural circuits can be identified from targeted connectomic analyses and specifically that the NOS-1 AC mediates long-range inhibition during night vision and is a major element of the RB pathway.

Highlights

IntroductionVision originates with rod photoreceptors. In mammals, rod output is conveyed to ganglion cells (GCs), the retinal projection neurons, by the rod bipolar (RB) cell pathway (Demb and Singer, 2015; Famiglietti and Kolb, 1975; Field et al, 2005) (Figure 1)
In dim light, vision originates with rod photoreceptors
Identified by serial block face electron microscopy (SBEM) analysis is a morphological match to the genetically-identified NOS-1 amacrine cell (AC), which we demonstrated to have physiological functions predicted by the ultrastructural analysis: it is an ON AC that provides GABAergic inhibition to AIIs and rod bipolar (RB)

Summary

Introduction

Vision originates with rod photoreceptors. In mammals, rod output is conveyed to ganglion cells (GCs), the retinal projection neurons, by the rod bipolar (RB) cell pathway (Demb and Singer, 2015; Famiglietti and Kolb, 1975; Field et al, 2005) (Figure 1). Absorption of photons by rods depolarizes RBs, which are ON cells. Three GC types in the mouse retina receive input from the RB pathway at or near visual threshold: the ON α GC and the OFF α and δ GCs, which exhibit high sensitivity to spatial contrast in the visual scene—similar to primate parasol cells —and project to the geniculocortical pathway (Ala-Laurila et al, 2011; Ala-Laurila and Rieke, 2014; Dunn et al, 2006; Grimes et al, 2018a; Grimes et al, 2015; Grimes et al, 2014b; Grimes et al, 2018b; Ke et al., 2014; Kuo et al, 2016; Murphy and Rieke, 2006, 2008).

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