However, the two forms of suppression differed. The depolarizing prepulse shifted the contrast response function rightward on the log-contrast axis and thereby suppressed the response to all contrasts, whereas the hyperpolarizing MK-2206 clinical trial prepulse suppressed mostly the response to high contrasts (Figure 3D). Furthermore, the time course of suppression differed for the two prepulses, as is illustrated most clearly at high contrast (Figure 3E). The depolarizing prepulse suppressed the spike rate during the entire responses, whereas the hyperpolarizing prepulse suppressed

the spike rate during the late phase of the response. To demonstrate further the physiological relevance of the suppressive effect of hyperpolarization, we used a purely visual paradigm to generate periods of hyperpolarization and depolarization. Sinusoidal contrast modulation of a spot was presented for 4 s. In one condition, the cell responded naturally for the first 2 s and then switched to a clamped state in which dynamic current injection prevented stimulus-evoked hyperpolarization (Figure 4A). In a second condition, the cell started in the clamped state and then switched to the unclamped state. At certain stimulus frequencies, the response was suppressed in the unclamped state, suggesting

that visually-evoked hyperpolarization normally suppresses firing during subsequent periods of depolarization. The level of www.selleckchem.com/products/ipi-145-ink1197.html response crossed over after 2 s, when the recording state switched on each trial (Figure 4B, gray line). We quantified the suppressive effect of contrast-evoked hyperpolarization on the firing rate as a function of temporal frequency. For the initial stimulus period, the response was suppressed

across a wide frequency range (Figure 4C). There was a significant decrease in firing in the unclamped state (expressed as a percentage difference Ribonucleotide reductase from firing in the clamped state) between 2 and 10 Hz (Figure 4E, p < 0.01 at each frequency). Thus, at the switch from mean luminance (i.e., 0% contrast) to high-contrast modulation, hyperpolarization preceding the initial depolarization was generally suppressive. After 2 s of stimulation, the initial firing rate adapted to a steady rate (illustrated for the 3 Hz stimulus; Figure 4B). At this point, the hyperpolarizations had a smaller suppressive effect on subsequent depolarization (Figure 4D) and depended more on the temporal frequency of modulation; suppression was observed in the 2–5 Hz range (Figure 4E; p < 0.01 for 2–3 Hz; p < 0.05 for 5 Hz; n = 10). Thus, the suppressive effect of hyperpolarization on subsequent firing could be evoked by visual contrast stimuli but was frequency dependent. We next turned to the mechanisms for the suppressive effects of depolarizing and hyperpolarizing prepulses.