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

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.

Neurotransmission plays contrasting roles in the maturation of inhibitory synapses on axons and dendrites of retinal bipolar cells

“…We did not immunolabel for GABA A α2 subunits because they are not localized to BCs (15). As found previously (4,19,20), our immunolabeling analysis showed that ON, but not OFF BC axon terminals express substantial amounts of GABA C receptors ( Fig. 1 B and D).…”

“…S1B). Previous electrophysiological studies suggest that GABA A receptors are abundant on axon terminals of BCs (4,19). Using subunit-specific antibodies, we determined the expression of GABA A α-subunits on the axons and dendrites of type 1 and 2 OFF CBCs, type 6 ON CBCs, and RBCs ( Fig.…”

“…How inhibition modifies neuronal output depends largely on the types of presynaptic interneurons making synapses onto a postsynaptic cell, and the location and densities of these synapses (1)(2)(3). Moreover, inhibitory receptor types with distinct transmitter affinities and kinetics present on the axon or dendrites of an individual neuron can critically shape its output (3)(4)(5)(6). Although much is known about how different inhibitory synapses shape the spatiotemporal activity patterns of mature neurons, it is less clear what factors regulate the expression of inhibitory receptors at these synapses during development in vivo.…”

ON cone bipolar cell axonal synapses in the OFF inner plexiform layer of the rabbit retina

“…Two non-exclusive functional implications arise. First, glycine receptor (glyR)-mediated, GABA receptor (GABAR)-mediated inhibition of bipolar cells may manifest different kinetics that combine with amacrine cell presynaptic release, such that GABA A R-and glyR-mediated inhibition predominantly control the magnitude of bipolar cell glutamate release, whereas GABA Cmediated inhibition controls the timing of bipolar cell glutamate release by increasing its transiency (Eggers and Lukasiewicz, 2011;Eggers and Lukasiewicz, 2006a;2006b;2010;Eggers et al, 2007). Crossover inhibition networks may appropriate these kinetic differences to increase the range and complexity of bipolar cell and ganglion cell responses.…”

GABAC Receptor-Mediated Inhibition Is Altered But Not Eliminated in the Superior Colliculus of GABAC ρ1 Knockout Mice

“…Elimination of 1 subunit expression leads to a complete loss of both GABA C R expression and GABA C R-mediated function (McCall et al 2002). As a consequence, retinal bipolar cells in GABA C 1 Null mice lack GABA C R-mediated feedback currents without compensatory changes in other inhibitory inputs (Eggers et al 2007) and related components of the electroretinogram are strongly enhanced in GABA C 1 Null mice (McCall et al 2002).…”