Under these conditions, locomotion was correlated with an increase in both ge and gi for all cells tested (Figures 3F and 3G; Table Birinapant cost 1). Interestingly, the balance of excitation and inhibition (E/I balance) was also modulated by behavioral state, reflected by a depolarization in the reversal potential of the visually evoked conductances (Figure 3H; Table 1). Together, both an increase in total conductance and a shift in the E/I balance toward excitation would be expected to produce larger

subthreshold depolarizations, consistent with our current-clamp data and the increased spiking during locomotion reported here and in previous studies (Figure S2; Ayaz et al., 2013 and Niell and Stryker, 2010). To examine whether the stationary and moving states are relevant for visual behavior, we trained mice to perform a visual detection task and analyzed their performance during the two conditions. Mice learned to lick for a water reward during the presentation PD0332991 research buy of drifting gratings of varying contrasts (low: 9%/16%; medium:

27%/50%; high: 81%/100%) and to withhold licking for the presentation of a gray screen (Figures 4A and 4B; Figures S4A and S4B). Injection of the GABAA-receptor agonist muscimol into V1 (n = 4) significantly impaired behavioral performance compared to saline controls (n = 4; Figure 4C; Figure S4C), indicating that the visual cortex was necessary for this task. Interestingly, locomotion was correlated with a significant increase in the hit rates for both low- and medium-contrast gratings. False alarm rates also increased during locomotion, though this effect was driven primarily by one animal and did not reach significance (Figure 4D; Table 2). An increase in hit rates could reflect an overall increase in licking

and not improved perception. To distinguish between these possibilities, we computed the discriminability (d′) for each contrast (Figure 4E; Table 2), a metric that is invariant to the behavioral criterion (Wickens, 2002). For each mouse tested, d′ was enhanced during locomotion for the low-contrast Astemizole condition; however, no significant effect was observed for the medium- and high-contrast conditions, likely reflecting a saturation of performance (Figure 4F; Table 2). Notably, moving trials were evenly distributed across the entire behavioral session (Figure S4D), and performance during the first and second halves of the sessions did not differ (p > 0.1, Wilcoxon signed-rank test). Thus, the improvement in d′ during movement did not reflect a correlation between locomotion and motivation. Here we present three main findings. First, we show large-amplitude, low-frequency membrane potential fluctuations in V1 during quiet wakefulness that are abolished during locomotion. This decrease in membrane potential variability results in reduced spontaneous firing rates during locomotion.