0001, Wilcoxon signed-rank tests; see Supplemental Experimental Procedures; Figure S2). These click here results, together with the increased sound-to-site coupling in the feedforward thalamocortical circuit, suggest that activation of auditory cortical PV+ neurons may facilitate bottom-up information flow in the feedforward direction. Previous studies have shown that optogenetic activation of PV+ neurons enhances stimulus feature selectivity and increases the signal-to-noise ratio (SNR) in cortical
neurons (Atallah et al., 2012, Lee et al., 2012, Sohal et al., 2009 and Wilson et al., 2012). In our study, light activation of PV+ neurons induced strong suppression of spontaneous firing and weak reduction of tone-evoked responses (mean percent suppression ± SEM = 31.77% ± 0.03% for spontaneous activity and
18.57% ± 0.03% for evoked activity; see Figures 5A and 5B for examples of peristimulus time histograms and receptive fields). This led to an increase in the detection SNR (mean detection SNR ± SEM = 6.13 ± 0.73 for “light-on” versus 3.17 ± 0.21 for “light-off” trials, p = 0.005 Wilcoxon signed-rank test, Figure 5C). In addition, PV+ neuron stimulation significantly narrowed receptive field bandwidths (p < 0.001, Wilcoxon signed-rank test) without changing response thresholds at the characteristic frequency (p = 0.79, Wilcoxon signed-rank test, Figure 5D). In sham-injected control mice not expressing ChR2, light stimulation PI3K inhibitor did not cause any significant change in response properties (Figure S3). To test the possibility that reduced spontaneous activity and increased detection SNR (Figures 5A–5C) aminophylline caused the observed increases in site-to-site coupling (Figure 3B), we randomly removed 20%–80% of spikes recorded in “light-off” trials to mimic the effects of stimulation of PV+ neurons with light and reconducted the Ising model analysis (see Experimental Procedures). The mean site-to-site coupling strength was not increased by the random reduction of spontaneous and evoked spikes (Figure 6A)
but rather was reduced in sites one node away within the same column (p < 0.001 for all comparisons, Bonferroni-corrected Wilcoxon signed-rank tests). No changes to between-site coupling two and three sites away within the column were seen (Bonferroni-corrected p > 0.05, Wilcoxon signed-rank tests), even with reductions in activity that were far larger than the suppression caused by PV+ neuron stimulation (∼32% suppression on average). There was also no change in sound-to-site coupling with these manipulations (Figure 6B). Finally, to determine if the altered site-to-site coupling strength was due to changes in evoked activity, we removed sound-evoked spikes and reconducted the analysis with only the (unaltered) spontaneous activity. The coupling strength was still higher during activation of the PV+ neurons (Figure 6C; Bonferroni-corrected p = 0.002 and p = 0.