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L. Duan, M. Hou, M. M. Slaughter; State Dependent NMDA-Mediated Light Responses in Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1412.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal ganglion cells possess AMPA and NMDA receptors, yet there is little evidence for NMDA synaptic signaling. Most of the ganglion cell excitatory synaptic currents can be blocked by AMPA receptor antagonists such as CNQX and NBQX. NMDA synaptic signals are evident when inhibition or uptake is blocked, suggesting that NMDA receptors are peri-synaptic and only evident when bipolar cell vesicular release is elevated. We studied the NMDA synaptic currents in the absence of enhanced presynaptic release.
Using whole cell voltage clamp protocols in the salamander retinal slice preparation, we evaluated the synaptic AMPA and NMDA currents under light adapted and dark adapted conditions.
Under control conditions in dark adapted retina, light evoked currents are blocked by CNQX and NBQX, but little altered by D-AP5 or other NMDA antagonists. However, in light adapted retina, D-AP5 significantly suppressed light-evoked currents, suggesting a large NMDA component. In both light adapted and dark adapted retina, strychnine, an ionotropic glycine receptor antagonist, enhanced almost exclusively the NMDA component of light-evoked currents, but did not prolong the decay kinetics of light responses. This suggests that the enhanced NMDA current was not produced by ‘spillover’ of glutamate release. In light adapted retina, with removal of magnesium from the extracellular solution, the light-evoked synaptic currents were dramatically augmented, increasing up to 10 fold over the control currents. Most of this current was blocked by D-AP5 but not by CNQX or NBQX. The small remaining EPSCs were blocked by AMPA antagonists. Magnesium free conditions also revealed spontaneous NMDA currents with 10% to 90% rise time of ~6 ms that were blocked by D-AP5. In light adapted retina, blocking the OFF pathway with CNQX sometimes led to enhanced NMDA mediated synaptic currents at light onset This may be due to crossover disinhibition between the OFF AMPA pathway and the ON NMDA pathway.
NMDA synaptic inputs to ganglion cells are state dependent; they can be unmasked by light adaptation, strychnine or removal of magnesium block. These results indicate that under certain conditions synaptic NMDA receptors can be activated without enhanced glutamate release.
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