We next recorded the responses to flashed gratings with the cortex inactivated. We silenced local cortical activity with a single electrical shock (300–400 μA, 200 μs, electrode negative) delivered through a low-impedance metal electrode placed in the upper layers of the cortex, typically within 500 μm of the patch pipette. This configuration has Lenvatinib nmr been shown to silence spiking for 50 ms in a 1–2 mm diameter region of cortex, while having little effect on visual responses in the LGN (Chung and Ferster, 1998). During inactivation, the cell in

Figure 1 showed only a 10% decrease in its response to high-contrast preferred gratings, suggesting that the thalamus contributed a large fraction of the excitatory inputs. Orientation tuning remained largely contrast invariant in that the width of tuning was similar at all contrasts (Figures 1G and 1H). As in the intact cortex, during inactivation, tuning widths at high and low contrasts were

similar across the population (mean σ 32° and 36°; paired t test, p = 0.12). And as observed previously (Chung and Ferster, 1998), the width of orientation tuning at each contrast was minimally changed by the cortical inactivation (compare Figure 1C and G; paired t test, p = 0.69 at 32%, p = 0.92 at 4%). Just prior to the response Pfizer Licensed Compound Library in vivo onset (0–30 ms), the shock caused a clear reduction in Vm variability. This reduction is visible when comparing the width of shading (SD) with and without shock (compare Figures 1E and 1I just after the start of the traces; summarized in Figure 2A). Once the visually evoked response began, CYTH4 however, variability in all cases returned to a level comparable to the flash-only condition (compare shading in Figures 1E and 1I at response peaks; summarized in Figure 2B). Kernel density estimates of the Vm distributions of four additional simple cells during cortical inactivation also showed increased Vm variability for low-contrast preferred gratings (Figure S2B). During inactivation, 25 out of 35 cells (∼72%) showed higher Vm variability for low-contrast preferred stimulation. Of the 26 neurons that originally showed higher Vm variability for low contrast preferred stimuli in the intact cortex, 21 cells (80%)

retained higher Vm variability after cortical inactivation. On average, Vm variability for low-contrast preferred stimuli was 20% greater than variability for high-contrast null stimuli (Figure 1J; p < 0.01, paired t test), compared to 22% for the intact cortex. The effects of inactivation on the SD ratio (low-contrast preferred/high-contrast null) are shown for individual neurons in Figure 2C, where the SD ratio for inactivated cortex is plotted against the SD ratio for intact cortex. The plot shows considerable scatter, as some cells show greater SD at high contrast than at low contrast in the intact cortex (upper left quadrant) and others show a greater SD at high contrast than at low contrast during inactivation (lower right quadrant).