Specific Wiring of Distinct Amacrine Cells in the Directionally Selective Retinal Circuit Permits Independent Coding of Direction and Size

Abstract

Local and global forms of inhibition controlling directionally selective ganglion cells (DSGCs) in the mammalian retina are well documented. It is established that local inhibition arising from GABAergic starburst amacrine cells (SACs) strongly contributes to direction selectivity. Here, we demonstrate that increasing ambient illumination leads to the recruitment of GABAergic wide-field amacrine cells (WACs) endowing the DS circuit with an additional feature: size selectivity. Using a combination of electrophysiology, pharmacology, and light/electron microscopy, we show that WACs predominantly contact presynaptic bipolar cells, which drive direct excitation and feedforward inhibition (through SACs) to DSGCs, thus maintaining the appropriate balance of inhibition/excitation required for generating DS. This circuit arrangement permits high-fidelity direction coding over a range of ambient light levels, over which size selectivity is adjusted. Together, these results provide novel insights into the anatomical and functional arrangement of multiple inhibitory interneurons within a single computational module in the retina.

Stimulus-dependent recruitment of lateral inhibition underlies retinal direction selectivity

“…The first is the GABAergic synapse onto presynaptic bipolar cells from other amacrine cell types (Hoggarth et al, 2015; Lee and Zhou, 2006). The second is direct GABAergic input onto SACs from non-SAC amacrine cells (Ding et al, 2016).…”

A Role for Synaptic Input Distribution in a Dendritic Computation of Motion Direction in the Retina

“…Second, blockade of GABA A signaling reduced DS in distal varicosities, primarily by increasing the dendritic response to inward motion. It is important to note that a bath application of gabazine not only affects SAC-SAC interactions, but will also affect wide-field amacrine cell inputs to SACs (Hoggarth et al, 2015) as well as the amount of glutamate released from bipolar cells, due to a relief of synaptic inhibition (Pei et al, 2015). However, GABA release from wide-field amacrine cells should not be DS, and the distribution of bipolar cell inputs on SACs allows them to maintain DS despite potential increases in glutamate release.…”

Functional Circuitry of the Retina

“…Additionally, electrical coupling within one class of DS ganglion cell amplifies the DS within the network and generates responses in separated neurons with constant lag times (Trenholm et al 2013). Size tuning is achieved separately from direction tuning via feedback from wide-field amacrine cells onto the presynaptic bipolar terminals of the DS cell (Hoggarth et al 2015). …”