Junctional conductance of retinal AII amacrine cell electrical synapses is decreased by NMDA receptors

Retinal AII amacrine cells are extensively coupled together by electrical synapses. Changes to the strength of these synapses affect how signals are routed through rod and cone retinal pathways during scotopic and photopic vision. Plasticity at these electrical synapses has not, to date, been characterized using electrophysiological approaches. We investigated the effects of NMDA receptor (NMDAR) activation on electrical coupling between AII cells using dual whole-cell patch-clamp electrophysiology in mouse retinal slices. NMDAR activation substantially decreased junctional conductance between AII cells. Relieving the Mg²⁺ block of NMDARs through bath application of Mg²⁺-free solution or by depolarizing AII cells to 0 mV reduced junctional conductance. Exogenous application of NMDA decreased conductance between cells, a decrease which was blocked by the non-selective NMDAR antagonist D-APV but not by Ro 25-6981, a selective GluN2B-NMDAR antagonist. Addition of either d-serine or glycine, both NMDAR coagonists, without NMDA, reduced the junctional conductance and the addition of either coagonist to NMDA-treated retinas further decreased conductance. Experiments were conducted in inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) knockout (KO) mice, serine racemase KO mice, and in wild-type (WT) mice with d-amino acid oxidase to reduce retinal d-serine levels. Under these conditions, the NMDAR-mediated decrease in conductance was maintained, indicating that endogenous d-serine is not necessary for NMDAR-mediated plasticity. These results demonstrate that NMDAR activation decreases electrical coupling between AII amacrine cells and suggest that both d-serine and glycine can serve as NMDAR coagonists for this plasticity. KEY POINTS: Retinal AII amacrine cells are extensively coupled together by electrical synapses. We show that NMDAR activation substantially decreased junctional conductance between AII cells. Relieving the Mg²⁺ block of NMDARs reduced junctional conductance. Addition of either d-serine or glycine, both NMDAR coagonists, reduced the junctional conductance. This research adds to existing evidence that NMDA receptors contribute to the plasticity of a key electrical synapse in the retina, the electrical synapse coupling AII amacrine cells together. The study adds to mounting evidence that NMDARs mediate plasticity at electrical as well as chemical synapses.