If the cortical circuit contributes to response variability, for example, through its recurrent

elements, then silencing the cortex should reduce that variability. To silence a small patch of the cortex around the recording electrode, we used local electrical click here stimulation (Chung and Ferster, 1998) and compared trial-to-trial variability before and during inactivation. Since electrical stimulation only affords a brief (∼100 ms) period during which the cortex is silenced, we measured variability and the effects of cortical silencing in the responses to briefly flashed gratings instead of drifting gratings. Before inactivating the cortex, we first examined whether orientation tuning of the Vm responses to flashed gratings was, in fact, contrast-invariant, as it is for drifting gratings. For the example cell in Figure 1, the width of orientation tuning was indeed similar across contrasts (Figure 1C), with only a slight narrowing at the lowest contrast (4%), as can

be seen in the normalized tuning curves of Figure 1D. Over the population, tuning width at high contrast (mean σ = 32°) was not significantly different than it was at low contrast (35°; paired t test, p = 0.20; n = 21). We next confirmed that the trial-to-trial variability in Vm responses increases with decreasing contrast for flashed gratings as it does for drifting gratings. This change in variability can be seen in Figure 1E Selumetinib nmr by comparing the trial-to-trial SD of the responses at high-contrast (gray and cyan shading) with the low-contrast SD (magenta shading). Detailed changes in the distribution of the response amplitudes in four additional cells are shown as kernel density estimates in Figure S2A (available online), where it can be seen that the Vm distributions evoked by low-contrast preferred stimuli were wider or more right-skewed than those evoked by high-contrast null stimuli. An indication of the contrast-dependent, but orientation-independent changes in PD184352 (CI-1040) variability can also be seen in the error

bars (SEM) of Figure 1C (compare circles). We quantified peak Vm variability for each stimulus condition as the SD of the Vm response in a 2.5 ms window centered on the peak of the mean Vm response. For the population of cells in Figure 1, the peak Vm SDs for high-contrast preferred stimuli, high-contrast null stimuli and low-contrast preferred stimuli were 3.66, 3.24, and 3.88 mV, similar to the values observed for drifting grating stimuli. Of the 35 cells studied, 26 showed higher Vm variability for low-contrast preferred stimuli (∼75%) than for high-contrast null stimuli. On average, peak Vm variability for low-contrast preferred stimuli was 22% greater than variability for high-contrast null stimuli (n = 35, p < 0.01, paired t test; Figure 1F).