Membrane potential variance is decreased and the remaining membrane potential fluctuations become less correlated in nearby

neurons (Figure 8A). The reduced membrane potential variance during whisking might help improve signal-to-noise ratios for sensory processing (Poulet and Petersen, 2008). During whisking, compared to quiet wakefulness, excitatory neurons on average depolarize by a few millivolts, PV neurons on average do not change membrane potential, 5HT3AR neurons depolarize strongly, and SST neurons hyperpolarize strongly (Gentet et al., 2010, 2012). Active sensing thus induces a significant reorganization of the L2/3 GABAergic neuronal network activity. The cortical state change during whisking is not affected by cutting the peripheral sensory nerves innervating

the whisker follicle, suggesting that the active desynchronized cortical state is internally PF-02341066 supplier driven by the brain (Poulet and Petersen, 2008; Poulet et al., 2012). The desynchronized cortical state in S1 during whisking is correlated to an increased firing rate of thalamocortical cells, is blocked by pharmacological inactivation of the thalamus, and can be mimicked by optogenetic stimulation of the thalamus (Figure 8B) (Poulet et al., 2012). Thus, an increase in thalamic AP firing rate drives important aspects of the cortical state change during whisking (Poulet et al., 2012). Neuromodulatory inputs are also likely to play a significant role in generating some desynchronized ERK signaling pathway inhibitors brain states (Constantinople and

Bruno, 2011; Lee and Dan, 2012) and modulating sensory processing (Edeline, 2012). Importantly, cortical sensory processing of the same peripheral stimulus differs strongly comparing and quiet and active cortical states (Fanselow and Nicolelis, 1999; Castro-Alamancos, 2004; Crochet and Petersen, 2006; Ferezou et al., 2006, 2007; Otazu et al., 2009; Niell and Stryker, 2010; Keller et al., 2012). In the mouse whisker system, a brief whisker deflection delivered during quiet wakefulness evokes a large-amplitude sensory response initially localized to the homologous cortical barrel column, which subsequently spreads across the barrel cortex and also excites the whisker motor cortex. However, the same stimulus delivered during active whisking evokes a smaller-amplitude response, which propagates over a much smaller cortical area (Figure 8C) (Crochet and Petersen, 2006; Ferezou et al., 2006, 2007). A similar suppression of sensory-evoked responses during active behaviors was observed in rat barrel cortex (Castro-Alamancos, 2004) and rat auditory cortex (Otazu et al., 2009). Increased firing rate of thalamocortical neurons resulting in short-term depression at thalamocortical synapses could be responsible for the decreased sensory response at the cortical level (Castro-Alamancos and Oldford, 2002; Otazu et al., 2009; Poulet et al., 2012).