Hamilton et al. (2013) first validate this approach as a viable method of analysis using the known effects of tonal stimulation and of the (vertical and horizontal) organization of cortical layers in the normal state of the animal. Then, under optical stimulation (and PV activation), the same analysis revealed a very different and

surprising picture: the vertical (across layer—and within column) connectivity was significantly enhanced, while the horizontal (within layer) interactions remained unchanged. This pattern effectively strengthened the coupling of the feedforward thalamocortical input to other cortical layers within a column. The Ising models are agnostic to the directionality of the correlations among neuronal learn more sites. For this, it is necessary to appeal to linear regression analyses that incorporate a time history of the responses to render an estimate of the spectrotemporal receptive fields (STRFs) of a given site relative to all other sites. These estimates confirmed

that upon optical stimulation of PV cells, superficial layers were indeed more affected by inputs from layer 4, with little within-layer changes. Finally, another fascinating result of PV stimulation is the HDAC inhibitor strong depression of spontaneous activity but relatively weaker reduction of stimulus responses, coupled with a narrowing of A1 tuning curves. These changes Levetiracetam effectively enhance the signal-to-noise ratio, significantly improving the

detection of a signal (tone) against the “quieter” spontaneous background, thus explaining how previous optogenetic activation of PV neurons enhanced stimulus feature selectivity in cortical neurons (Atallah et al., 2012). The importance of the Hamilton et al. (2013) findings can be best appreciated when viewed in the context of previous studies. For instance, the effects of PV stimulation are remarkably consistent with those induced during behavioral task performance by attention and expectations on sensory cortical responses, including the suppressive effects of sensory responses (Otazu et al., 2009) and the hypotheses implicating inhibitory interneurons in mediating attention effects (Mitchell et al., 2007). The suppressive effects are also seen during short-term memory and expectation (Jaramillo and Zador, 2011, Linke et al., 2011 and Wiggs and Martin, 1998). PV inhibitory neurons are ubiquitous in the brain. Recent recordings of optogenetically tagged PV cell responses in mouse prefrontal cortex during natural foraging behavior have revealed a strong correlation between their responses and specific behavioral events “leaving a reward zone” (Pi et al., 2013). This suggested a role for these cells in controlling the flow of information (especially pyramidal cell outputs) during behavioral events.