Different glutamate sources and endogenous co‐agonists activate extrasynaptic NMDA receptors on amacrine cells of the rod pathway microcircuit

Abstract The NMDA receptors (NMDARs) expressed by AII and A17 amacrine cells, the two main inhibitory interneurons of rod pathway microcircuit in mammalian retina, are exclusively extrasynaptic, activated ambient levels glutamate, molecularly distinct, with amacrines expressing GluN2B‐ GluN2A‐containing receptors, respectively. This important sensory thus provides a unique model to study activation function extrasynaptic NMDARs. Here, we investigated sources glutamate endogenous co‐agonists ( d ‐serine or glycine) that activate these distinct populations With acute slices from rat used whole‐cell voltage‐clamp recording measurement current noise monitor NMDAR activity. Pre‐incubation retina bafilomycin A1 (an inhibitor neurotransmitter uptake into synaptic vesicles) abolished NMDAR‐mediated AII, but not amacrines, suggesting vesicular source activates NMDARs, whereas non‐vesicular l ‐methionine sulfoximine glutamine synthetase) also neuronal glial Enzymatic breakdown reduced is co‐agonist at Our results reveal characteristics differential independent likely provide specific contributions signal processing plasticity cellular components microcircuit.