Presynaptic inhibition differentially shapes transmission in distinct circuits in the mouse retina

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Abstract
Diverse retinal outputs are mediated by ganglion cells that receive excitatory input from distinct classes of bipolar cells (BCs). These classes of BCs separate visual signals into rod, ON and OFF cone pathways. Although BC signalling is a major determinant of the ganglion cell-mediated retinal output, it is not fully understood how light-evoked, presynaptic inhibition from amacrine cell inputs shapes BC outputs. To determine whether differences in presynaptic inhibition uniquely modulate BC synaptic output to specific ganglion cells, we assessed the inhibitory contributions of GABA(A), GABA(C) and glycine receptors across the BC pathways. Here we show that different proportions of GABA(A) and GABA(C) receptor-mediated inhibition determined the kinetics of GABAergic presynaptic inhibition across different BC classes. Large, slow GABA(C) and small, fast GABA(A) receptor-mediated inputs to rod BCs prolonged light-evoked inhibitory postsynaptic currents (L-IPSCs), while smaller GABA(C) and larger GABA(A) receptor-mediated contributions produced briefer L-IPSCs in ON and OFF cone BCs. Glycinergic inhibition also varied across BC class. In the rod-dominant conditions studied here, slow glycinergic inputs dominated L-IPSCs in OFF cone BCs, attributable to inputs from the rod pathway via AII amacrine cells, while rod and ON cone BCs received little and no glycinergic input, respectively. As these large glycinergic inputs come from rod signalling pathways, in cone-dominant conditions L-IPSCs in OFF cone bipolar cells will probably be dominated by GABA(A) receptor-mediated input. Thus, unique presynaptic receptor combinations mediate distinct forms of inhibition to selectively modulate BC outputs, enhancing the distinctions among parallel retinal signals.