Fig. 4.

Proposed model illustrating the regulation of coagonist in the inner plexiform layer. Müller cell processes surrounding the bipolar-ganglion cell synapse contribute d-serine at RGC synaptic sites, while glycine transporters (GlyT1), expressed in Müller and amacrine cells, restrict glycine to extrasynaptic sites. NMDAR activation requires glutamate and a coagonist. Gated NMDA and AMPARs indicated by arrow. A: in the absence of light stimulation, moderate activation of Müller cell AMPARs by ambient glutamate causes the release of d-serine through an unknown mechanism. B: light-evoked glutamate release from bipolar cell terminals activates additional AMPARs, evoking currents in RGCs and also causing further d-serine release from Müller cells. d-Serine recruits additional synaptic NMDARs for activation via glutamate. C: pressure-ejected or bath-applied NMDA largely activates extrasynaptic NMDARs occupied by glycine, while synaptic activation is limited by low levels of d-serine.