@entity143 receptors (NMDARs) are tetrameric protein complexes usually comprising two @entity4474 and two NR2 subunits. Different combinations of four potential NR2 subunits (NR2A-D) confer diversity in developmental expression, subsynaptic localization, and functional characteristics, including affinity for neurotransmitter. @entity4319 -containing NMDARs, for example, exhibit relatively high affinity both for @entity2227 and the coagonist @entity2228 . Although multiple NMDAR subtypes can colocalize at individual synapses, particular subtypes often mediate inputs from distinct functional pathways. In @entity2479 cells (RGCs), NMDARs contribute to synaptic responses elicited by light stimulus onset ("ON") and offset ("OFF"), but roles for particular NMDAR subtypes, and potential segregation between the ON and OFF pathways, have not been explored. Moreover, elements in the retinal circuitry release two different NMDAR coagonists, @entity2228 and @entity7343 , but the effects of endogenous coagonist release on the relative contribution of different NMDAR subtypes are unclear. Here, we show that coagonist release within the retina modulates the relative contribution of different NMDARs in the ON pathway of the @entity35 retina. By pharmacologically stimulating functional pathways independently in acute slices and recording synaptic responses in RGCs, we show that ON inputs, but not OFF inputs, are mediated in part by NMDARs exhibiting @entity4319 -like pharmacology. Furthermore, suppressing release of NMDAR coagonist reduces NMDAR activation at ON synapses and increases the relative contribution of these putative @entity4319 -containing receptors. These results demonstrate direct evidence for evoked coagonist release onto NMDARs and indicate that modulating coagonist release may regulate the relative activation of different NMDAR subtypes in the ON pathway.

Coagonist release modulates @entity143 receptor subtype contributions at synaptic inputs to XXXX cells.

@entity7343 :: ('CHEBI:16523', 'Chemical') :: ['d-serine'] @entity4319 :: ('24410(Tax:10116)', 'Gene') :: ['NR2B'] @entity2227 :: ('CHEBI:29987', 'Chemical') :: ['glutamate'] @entity2228 :: ('CHEBI:57305', 'Chemical') :: ['glycine'] @entity2479 :: ('MESH:D012173', 'Disease') :: ['retinal ganglion'] @entity4474 :: ('24408(Tax:10116)', 'Gene') :: ['NR1'] @entity143 :: ('CHEBI:6121', 'Chemical') :: ['NMDA'] @entity35 :: ('10116', 'Species') :: ['rat']
@entity2479 :: (MESH:D012173,Disease) :: ['retinal ganglion']
