Excitatory effect of group I metabotropic glutamate receptor activation on cultured rat retinal ganglion cells

This study addresses the neuromodulation mediated by Gq-coupled group I metabotropic glutamate receptors (mGluRs) on retinal ganglion cells (RGCs). RGCs were isolated and purified by an immunopanning procedure. An RGC-astroglia co-culture system was employed to maintain and nurture RGCs in vitro . Using whole-cell patch-clamp recordings, an excitatory effect of the group I mGluR agonist dihydroxyphenylglycine (DHPG) on RGCs was discovered. Unlike ionotropic glutamate receptors (iGluRs) that gate cation influx as an excitatory signal, activation of group I mGluRs suppressed a constitutively active outward K+ current and thus depolarized the neurons, accompanied by an increase in the membrane input resistance. The background K+ current reduced by DHPG showed pH-sensitivity but was insensitive to extracellular Cs+ at millimolar concentration, reminiscent of the recently discovered TASK channels that can be inhibited by receptor signaling through Gq proteins. Firing properties of RGCs in the co-culture system were examined and used as criteria for classification. Application of DHPG differentially affected RGC spiking behaviour depending on the intrinsic firing patterns. Biophysical mechanisms responsible for the different discharge patterns and the selective modulation by DHPG remain mysterious but data is presented suggesting that additional ion channels, activated during spike activity, are also influenced by group I mGluRs.; The characterization of a group I mG1uR-mediated excitation in RGCs compliments the current working scheme of excitatory synaptic transmission from bipolar cells to RGCs in the inner retina. This work should also inspire efforts to elucidate the distribution of group I mGluRs on RGC dendrites and encourage studies of mG1uR function in more physiologically-relevant retinal preparations. While recognizing the limitations of in vitro work, the current study demonstrates the use of the RGC-astroglia co-culture system as a reduced model for exploring receptor pharmacology and neuromodulation in RGCs.