, 2010 and Haider et al., 2013), which is partly attributed SAHA HDAC in vitro to increased inhibition in the cortical network (Haider et al., 2010, Adesnik et al., 2012, Nienborg et al., 2013 and Vaiceliunaite et al., 2013). However, when averaged over the entire stimulation period, we found that costimulation of the surround with either natural or phase-scrambled movies slightly depolarized the median absolute Vm in immature and mature mice (Figures 3B and 3H; p = 0.017 and p <

0.0001, respectively; Friedman’s test). Because it is unclear how such small average differences in Vm could contribute to changes in the spiking response selectivity, we focused our analysis on how Vm temporal dynamics are altered by surround stimulation. We quantified moment-to-moment differences in Vm between RF and full-field stimulation for each neuron (ΔVm = VmRF+surround − VmRF; see Experimental Procedures). Both natural and phase-randomized surround

stimuli induced hyperpolarizing (negative ΔVm) and depolarizing (positive ΔVm) Vm changes relative to RF stimulation alone (Figures 3C and 3G). Plotting the median ΔVm of each cell against its average change in firing rate revealed Alisertib cell line that ΔVm was strongly correlated with the firing rate suppression during full-field stimulation in mature, but not in immature mice (Figures 3D and 3I; see figure legend for details). Moreover, the distribution of ΔVm was shifted to more negative values during natural than phase-randomized surround stimulation in mature V1 (Figure 3D, p = 0.027, Wilcoxon rank sum test), but not in immature V1 (Figure 3I, p = 0.6, Wilcoxon rank sum test). How could relatively small differences in ΔVm between natural and phase-randomized surround stimulation lead to pronounced differences in firing rate suppression check incurred by these surround stimuli in mature V1? To address this question, we determined the dependency of ΔVm on the particular membrane potential value (relative to spike threshold) elicited by the RF stimulus at each time point during movie presentation (VmRF). Strikingly, in both age groups, ΔVm exhibited a negative linear dependency on membrane depolarization during RF stimulation:

neurons were relatively most hyperpolarized during RF + surround stimulation (negative ΔVm) specifically at times when VmRF was closest to spiking threshold (Figures 3E and 3J). Which mechanisms underlie the pronounced surround-induced relative hyperpolarization when the Vm is most depolarized during RF stimulation? Surround stimulation has been shown to increase synaptic inhibition (Haider et al., 2010, Haider et al., 2013 and Adesnik et al., 2012). We therefore tested the influence of chloride (Cl−)-mediated conductances on the inverse relationship between ΔVm and VmRF. We performed whole-cell recordings using an elevated Cl− concentration in the intracellular solution ([Cl−]i, see Experimental Procedures) to modify the reversal potential of GABAA-mediated conductances (Figure 4A).