Abstract
Abstract: :
Purpose: NMDA receptors (NMDARs) are expressed by retinal ganglion cells (RGCs) in all species studied to date, but a specific role for NMDARs in RGC synaptic processing remains unclear. Physiological evidence indicates that NMDARs on rat RGCs are located extrasynaptically and, consequently, are more sensitive to changes in release probability (Chen and Diamond, 2002). The present study tested the hypothesis that their extrasynaptic localization enables NMDARs to expand the dynamic range of RGC light responses. Methods: Whole–cell patch clamp recordings were made from RGCs of acute slices of P17–21 rat retina at 35ºC. Light–evoked responses were recorded under voltage and current clamp in the presence of GABA–A, GABA–C and glycine receptor antagonists and elicited with a 50 µm–diameter spot of 500–nm light centered on the photoreceptors above the recorded RGC. Results:Light evoked excitatory postsynaptic currents (EPSCs) exhibited both AMPA receptor (AMPAR)– and NMDAR–mediated components. The NMDAR antagonist CPP blocked the slow component of light–evoked EPSCs. Application of Ro25–691 (10 µM), a specific antagonist of NR2B–containing NMDARs, partially blocked the slow component of the light evoked EPSCs. Ro25–691 completely blocked the NMDAR–medicated component of miniature EPSCs that was revealed when glutamate uptake was reduced with 10 µM TBOA, a glutamate transporter antagonist. Spike responses, recorded under whole–cell current clamp, indicated that rat RGCs convert injected current to spike frequency in a linear fashion and encode changes in light intensity over a 2 log unit range of light stimulus intensity. When NMDARs were blocked by CPP, the light–evoked spike frequency was reduced most in responses to stronger light stimuli, resulting in a decrease in the dynamic range of the RCG light response. Conclusion: These results suggest that NMDARs expand the dynamic range of RCGs to light stimuli, perhaps due to their extrasynaptic localization.
Keywords: ganglion cells • synapse • receptors