The roles of ionotropic glutamate receptors along the On and Off signaling pathways in the light-adapted mouse retina

Although the locations of glutamate receptors along the On and Off pathways have been determined, how these receptors modulate the retinal outputs―the light-evoked and spontaneous activities of individual ganglion cells―is not fully understood in the mouse retina. Specifically, how these receptors mediate On and Off responses of retinal ganglion cells in mouse retina under light adaptation remains unknown. Since mouse retina has become a powerful model for vision research, the functions of glutamate receptors along the On and Off pathways in mouse need to be determined. In the current study, the light-evoked and spontaneous excitatory postsynaptic currents (light-evoked EPSCs and sEPSCs) from On, Off and On–Off retinal ganglion cells (RGCs) were recorded using whole-cell patch-clamp recordings to assess how NMDA and AMPA/KA receptors modulate the retinal outputs of RGCs in the light-adapted mouse retina. We found NMDA and AMPA/KA played different roles in light-evoked EPSCs along On and Off pathways in light-adapted mice retinas. Both NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (AP-5) and AMPA/KA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) acted on RGCs to reduce On responses of ganglion cells while they acted on Off-cone bipolar cells and/or ganglion cells to mediate Off responses of RGCs. Co-application of AP-5 and CNQX completely eliminated the Off responses in majority of RGCs, indicating that both NMDA and AMPA/KA receptors are critical for light signaling along the cone-driven Off pathways in the light-adapted mouse retina.

Research highlights
► We studied the functions of NMDA and AMPA/KA in light-adapted mouse retinas.
► NMDA and AMPA/KA differentially affect the outputs of retinal ganglion cells (RGCs).
► Antagonists of NMDA and AMPA/KA (AP-5, CNQX) act on RGCs to reduce On responses.
► AP-5 and CNQX affect Off-cone bipolar cells and RGCs to mediate Off responses.
► AP-5 together with CNQX eliminated the Off responses in majority of RGCs.