Distinct expressions of contrast gain control in parallel synaptic pathways converging on a retinal ganglion cell

Visual neurons adapt to increases in stimulus contrast by reducing their response sensitivity and decreasing their integration time, a collective process known as ‘contrast gain control.’ In retinal ganglion cells, gain control arises at two stages: an intrinsic mechanism related to spike generation, and a synaptic mechanism in retinal pathways. Here, we tested whether gain control is expressed similarly by three synaptic pathways that converge on an OFF α/Y‐type ganglion cell: excitatory inputs driven by OFF cone bipolar cells; inhibitory inputs driven by ON cone bipolar cells; and inhibitory inputs driven by rod bipolar cells. We made whole‐cell recordings of membrane current in guinea pig ganglion cells in vitro. At high contrast, OFF bipolar cell‐mediated excitatory input reduced gain and shortened integration time. Inhibitory input was measured by clamping voltage near 0 mV or by recording in the presence of ionotropic glutamate receptor (iGluR) antagonists to isolate the following circuit: cone → ON cone bipolar cell → AII amacrine cell → OFF ganglion cell. At high contrast, this input reduced gain with no effect on integration time. Mean luminance was reduced 1000‐fold to recruit the rod bipolar pathway: rod → rod bipolar cell → AII cell → OFF ganglion cell. The spiking response, measured with loose‐patch recording, adapted despite essentially no gain control in synaptic currents. Thus, cone bipolar‐driven pathways adapt differently, with kinetic effects confined to the excitatory OFF pathway. The ON bipolar‐mediated inhibition reduced gain at high contrast by a mechanism that did not require an iGluR. Under rod bipolar‐driven conditions, ganglion cell firing showed gain control that was explained primarily by an intrinsic property.