Abstract
Purpose:
To examine the circuits regulated by metabotropic glycine receptors in the rat retina and explore the mechanism of action.
Methods:
Whole-cell recordings were made from rat retinal ganglion cells in the whole-mount retina using current clamp and voltage clamp procedures. Retinas were taken from Sprague Dawley rats ages P30-60 and dark adapted for 30 minutes prior to recording. The metabotropic glycine receptor was activated by applying low concentrations of glycine. Strychnine was continuously applied in these experiments to eliminate activation of ionotropic glycine receptors. Synaptic output of bipolar cells was measured by recording the light-evoked EPSCs in ganglion cells.
Results:
The putative metabotropic glycine receptor has previously been shown to inhibit calcium currents in third order neurons in the isolated rat retina preparation. To further investigate this effect, we utilized a whole-mount retina stimulated with a 1 second green light stimulus to measure the physiological response to 10 μM glycine in the presence of 1-10μM strychnine. Cesium and QX 314 were included in the intracellular pipette solution in order to block potassium and sodium currents in ganglion cells, allowing the recording of bipolar cell excitatory output. Application of glycine/strychnine augmented the ON response. A possible mechanism might be that metabotropic glycine receptor activation reduced the output of amacrine cells. GABA receptor blockers also enhanced the output of bipolar cells and occluded the effects of glycine/strychnine.
Conclusions:
The results indicate that metabotropic glycine receptors can regulate GABAergic amacrine cell feedback to bipolar cells. The likely mechanism is that when metabotropic glycine receptors are activated, they suppress L-type calcium channels in amacrine cells, and thereby reduce feedback inhibition at bipolar cell terminals. This is opposite to the effect of metabotropic glycine receptors in salamander retina, where their activation caused a suppression of glutamate release.
Keywords: 728 synapse •
508 electrophysiology: non-clinical