“Silent” NMDA Synapses Enhance Motion Sensitivity in a Mature Retinal Circuit

Abstract

Summary Retinal direction-selective ganglion cells (DSGCs) have the remarkable ability to encode motion over a wide range of contrasts, relying on well-coordinated excitation and inhibition (E/I). E/I is orchestrated by a diverse set of glutamatergic bipolar cells that drive DSGCs directly, as well as indirectly through feed-forward GABAergic/cholinergic signals mediated by starburst amacrine cells. Determining how direction-selective responses are generated across varied stimulus conditions requires understanding how glutamate, acetylcholine and GABA signals are precisely coordinated. Here, we use a combination of paired patch-clamp recordings, serial EM and large-scale multi-electrode array recordings to show that a single high-sensitive source of glutamate is processed differentially by starbursts via AMPA receptors and DSGCs via NMDA receptors. We further demonstrate how this novel synaptic arrangement enables DSGCs to encode direction robustly near threshold contrasts. Together, these results reveal a space-efficient synaptic circuit model for direction computations, in which ‘silent’ NMDA receptors play a critical roles.

Cholinergic excitation complements glutamate in coding visual information in retinal ganglion cells

“…), probably via NMDA receptors to ensure robust direction computation (Sethuramanujam et al . ). BP(3/4)‐II provides exclusive excitation to DSGCs via AMPA receptors and possibly via NMDA receptors.…”

“…By contrast, recent studies examining DSGCs in mouse and rabbit retina have suggested that under conditions of low stimulus contrast, ACh can be the primary source of excitation (Sethuramanujam et al 2016;Brombas et al 2017). Under low contrast conditions, a common set of high sensitivity bipolar cells appear to drive starbursts via AMPA receptors and DSGCs via NMDA receptor-dominated synapses (Sethuramanujam et al 2017). As NMDA receptors alone are unable to strongly depolarize ganglion cells, bipolar cell inputs to ganglion cells remain silent in the absence of cholinergic excitation (Sethuramanujam et al 2016).…”

“…8). However, these common bipolar cells, which have high sensitivity, drive DSGCs predominantly via silent NMDA receptors but drive starbursts via AMPA receptors (Sethuramanujam et al 2017). Thus under low-contrast conditions, where AMPA receptor-mediated inputs from low-sensitivity bipolar cells (BP5-II in Fig.…”

“…The ON starbursts and ON dendrites of DSGCs receive depolarizing glutamate excitation (i.e. AMPA receptor activity) from distinct bipolar cells Sethuramanujam et al 2017). BP5-I, a bipolar cell with high-contrast sensitivity, probably provides AMPA receptor-mediated excitation to ON starbursts while providing NMDA receptor-mediated excitation to ON dendrites of DSGCs (Sethuramanujam et al 2017).…”

“…Under low contrast conditions, a common set of high sensitivity bipolar cells appear to drive starbursts via AMPA receptors and DSGCs via NMDA receptor‐dominated synapses (Sethuramanujam et al . ). As NMDA receptors alone are unable to strongly depolarize ganglion cells, bipolar cell inputs to ganglion cells remain silent in the absence of cholinergic excitation (Sethuramanujam et al .…”