In order to average across cells, each of which had slightly different Vrest and input resistance (Rin), Transferase inhibitor we replotted the data as a function of Vm during the prepulse (Figure 1C). The number of spikes evoked by the test pulse peaked when the prepulse was near the average Vrest and was suppressed

by prepulses that evoked hyperpolarizations and depolarizations within the physiological range (−10 mV to +20 mV relative to Vrest) (Figure 1D). To test the physiological relevance of the prepulses in the above current-injection experiment, we substituted the test pulse with a visual stimulus: a spot (0.4 mm diameter) that decreased contrast by 100% (i.e., the mean luminance switched to black). check details The number of spikes evoked by the contrast stimulus peaked when the prepulse was near Vrest and was suppressed by prepulses that evoked hyperpolarizations or

depolarizations (Figures 1E, 1G, and 1H). Thus, prepulses evoked by current injection at the soma suppress subsequent visually-evoked, synaptically-driven responses originating at the dendrites. We tested whether the prepulse and associated change in Vm and firing rate could have fed back through the circuitry (i.e., through gap junctions with inhibitory amacrine cells) to suppress the visual response. We injected either hyperpolarizing or depolarizing prepulses in current clamp, as above, and then switched to voltage clamp to record contrast-evoked synaptic currents (Vhold near Vrest, ∼−65 mV). Under these conditions, the prepulses had essentially no effect on the synaptic input (Figure 1F), suggesting that the effect of prepulses on the firing response to contrast depends on intrinsic properties of the ganglion cell and does not involve feedback onto presynaptic neurons. Depolarization and hyperpolarization typically stimulate different sets of voltage-gated channels,

and so it seemed likely Adenosine that the suppressive effects observed by depolarizing and hyperpolarizing prepulses depended on separate mechanisms. Indeed, the time course of suppression differed after the two classes of prepulse. In most experiments below, prepulse current injections were designed to change Vm within the physiological range: +400 pA versus −280 pA, which typically evoked +15 mV versus −10 mV changes in Vm. A depolarizing prepulse suppressed firing to the test pulse across the entire test-pulse duration, whereas a hyperpolarizing prepulse suppressed only the late firing to the test pulse (Figure 2A). The time course of the suppressive effects can be visualized in cumulative firing-rate plots for each stimulus (Figure 2A, inset). We performed a similar analysis in the case where visual contrast replaced the test pulse. In this case, the depolarizing prepulse suppressed firing to contrast across the duration of the response, whereas a hyperpolarizing prepulse suppressed primarily the late firing (Figure 2B).