PURPOSE: To understand whether spontaneous excitatory postsynaptic currents (sEPSCs) and evoked excitatory postsynaptic currents (EPSCs) are mediated by both AMPA receptors (AMPARs) and NMDA receptors (NMDARs) in ganglion cells of the rat retinal slice preparation. In addition, to determine whether NMDARs are located at a distance from the site of synaptic release.
METHODS: Patch-clamp recordings were made from neurons in the ganglion cell layer of acute slices of rat retina. Evoked responses were elicited with either a bipolar electrode positioned in the distal part of the inner layer, or using full-field green light stimulate photoreceptors.
RESULTS: Both electrically- and light-evoked EPSCs exhibited both NMDAR- and AMPAR-mediated components. However, sEPSCs were mediated solely by AMPARs. The effect of low-affinity, competitive receptor antagonists indicated that NMDARs encounter less glutamate than AMPARs during evoked synaptic responses. Reducing glutamate uptake or changing the probability of release, by changing either extracellular calcium or light stimulus intensity, preferentially affected the NMDAR component in evoked EPSCs; reducing uptake revealed an NMDAR component in sEPSCs.
CONCLUSIONS: The results suggest that NMDARs on neurons in the ganglion cell layer are located extrasynaptically. Under physiological conditions, changing light contrast preferentially enhanced NMDAR-mediated components. Glutamate transporters prevent NMDAR activation by transmitter released from a single vesicle and limit their activation during evoked responses.