The existence of discrete modes also makes the surprising prediction that neurons belong to the same mode should have very similar tuning. This is also consistent with previous observations: both silicon probe and optical recordings have shown that neighboring neurons in superficial auditory cortex can have strongly correlated activity, but that the probability of seeing these high correlations falls rapidly with interneuronal distance (Sakata and Harris, 2009; Rothschild et al., 2010). For

technical reasons, with two-photon microscopy one can only image the superficial layers of cortex. And there are reasons to believe that the organization revealed by this study is in fact specific to the superficial layers. As mentioned above, an organization of discrete local assemblies is consistent with previous reports of sparse activity in superficial cortex, and the existence of strong correlations between local but not distal pairs Ibrutinib price (Sakata and Harris, 2009; Rothschild et al., 2010). However, these phenomena are not observed

in deep layers of cortex, where activity is less sparse, and correlations weaker and less dependent on distance. This suggests that deep layer activity Epigenetic activity inhibition has a different organization, with smooth variation across the cortical surface rather than discrete localized modes (Sakata and Harris, 2009). These differences in activity patterns might in turn arise from differences in connectivity and physiology between cortical layers. For example, lateral excitatory connections in the superficial layers fall off rapidly within a distance of a few hundred microns (Oswald and Reyes, 2008),

while deep-layer connectivity extends much further (Schubert et al., 2007). The fact that only a handful of response modes could be evoked within the 200 μm area scanned by the two-photon microscope does not mean that the entire auditory cortex has such a limited repertoire. Indeed, in different recordings—including multiple fields of view in a single mouse—the sets of stimuli activating the response modes were different. This suggests that any one stimulus evokes many response modes spread over the superficial auditory cortex, with the precise combination of modes activated no depending on the stimulus (Figure 1C). Thus, the picture that emerges from this study is quite similar to our original assumption about population coding (Figure 1A) but with the fundamental coding unit being not a single neuron, but an assembly that inexorably fires together. In support of this idea, Bathellier et al. (2012) found that when they pooled together all their recordings, the population activity patterns produced could not only accurately decode a large number of stimuli, but predict the behavioral discriminations made by mice. One of the reasons that this picture is counterintuitive is that it seems inefficient.