GABA(B) receptor feedback regulation of bipolar cell transmitter release.
GABAergic amacrine cell feedback to bipolar cells in retina has been described, activating both GABA(A) and GABA(C) receptors. We explored whether metabotropic GABA(B) receptors also participate in this feedback pathway. CGP55845, a potent GABA(B) receptor antagonist, was employed to determine the endogenous role of these receptors. Ganglion cell EPSCs and IPSCs were monitored to measure the output of bipolar and amacrine cells. Using the tiger salamander slice preparation, we found that GABA(B) receptor pathways regulate bipolar cell release directly and indirectly. In the direct pathway, the GABA(B) receptor antagonist reduces EPSC amplitude, indicating that GABA(B) receptors cause enhanced glutamate release from bipolar cells to one set of ganglion cells. In the indirect pathway, the GABA(B) receptor antagonist reduces EPSC amplitude in another set of ganglion cells. The indirect pathway is only evident when GABA(A) receptors are inhibited, and is blocked by a glycine receptor antagonist. Thus, this second feedback pathway involves direct glycine feedback to the bipolar cell and this glycinergic amacrine cell is suppressed by GABAergic amacrine cells, through both GABA(A) and GABA(B) but not GABA(C) receptors. Overall, GABA(B) receptors do contribute to feedback regulation of bipolar cell transmitter release. However, unlike the ionotropic GABA receptor pathways, the metabotropic GABA receptor pathways act to enhance bipolar cell transmitter release. Furthermore, there are three discrete subsets of bipolar cell output regulated by GABA(B) receptor feedback (direct, indirect and null), implying three distinct, non-overlapping bipolar cell to ganglion cell circuits.
Song
Yunbo
Y
Department of Physiology & Biophysics, Center for Neuroscience, 124 Sherman Hall, 3435 Main Street, Buffalo, NY 14214, USA. ysong8@buffalo.edu
Slaughter
Malcolm M
MM
D000557:Ambystoma / Q000502:physiology*; D000818:Animals; D025461:Feedback, Physiological / Q000502:physiology*; D018756:GABA Antagonists / Q000494:pharmacology; D010721:Phosphinic Acids / Q000494:pharmacology*; D011412:Propanolamines / Q000494:pharmacology*; D018080:Receptors, GABA-B / Q000502:physiology*; D051245:Retinal Bipolar Cells / Q000502:physiology*
D018756:GABA Antagonists; D010721:Phosphinic Acids; D011412:Propanolamines; D018080:Receptors, GABA-B; C085075:CGP 55845A