Cone signals divide into parallel ON and OFF bipolar cell pathways, which respond to objects brighter or darker than the background and release glutamate onto the corresponding type of ganglion cell. It is assumed that ganglion cell excitatory responses are driven by these bipolar cell synapses. Here, we report an additional mechanism: OFF ganglion cells were driven in part by the removal of synaptic inhibition (

Retinal ganglion cells fire spikes to an appropriate contrast presented over their receptive field center. These center responses undergo dynamic changes in sensitivity depending on the ongoing level of contrast, a process known as "contrast gain control." Extracellular recordings suggested that gain control is driven by a single wide-field mechanism, extending across the center and beyond, that depends on inhibitory interneurons: amacrine cells. However, recordings in salamander suggested that the excitatory bipolar cells, which drive the center, may themselves show gain control independently of amacrine cell mechanisms. Here, we tested in mammalian ganglion cells whether amacrine cells are critical for gain control over the receptive field center. We made extracellular and whole-cell recordings of guinea pig Y-type cells in vitro and quantified the gain change between contrasts using a linear-nonlinear analysis. For spikes, tripling contrast reduced gain by ϳ40%. With spikes blocked, ganglion cells showed similar levels of gain control in membrane currents and voltages and under conditions of low and high calcium buffering: tripling contrast reduced gain by ϳ20 -25%. Gain control persisted under voltage-clamp conditions that minimize inhibitory conductances and pharmacological conditions that block inhibitory neurotransmitter receptors. Gain control depended on adequate stimulation, not of ganglion cells but of presynaptic bipolar cells. Furthermore, horizontal cell measurements showed a lack of gain control in photoreceptor synaptic release. Thus, the mechanism for gain control over the ganglion cell receptive field center, as measured in the subthreshold response, originates in the presynaptic bipolar cells and does not require amacrine cell signaling.

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.

The mechanism by which an applied electric field stimulates cardiac tissue far from the stimulating electrodes is not wholly understood. One possible mechanism relates the curving cardiac fibers to the induced membrane currents and transmembrane potentials. However, we lack a qualitative understanding of where these areas of polarization will occur when an electric field is applied to a sheet of cardiac tissue with curving fibers. In our study, we derive an analytical model for the transmembrane potential, dependent on the gradient of the fiber angle theta, for a two-dimensional passive sheet of cardiac tissue exhibiting various fiber geometries. Unequal anisotropy ratios are crucial for our results. We compare the results from our analytical solution to a numerical calculation using the full bidomain model. The results of our comparison are qualitatively consistent, albeit numerically different. We believe that our analytical approximation provides a reliable prediction of the polarization associated with an electric field applied to cardiac tissue with any fiber geometry and a qualitative understanding of the mechanisms behind the virtual electrode polarization.

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