These studies indicate a segregation of—potentially autonomous—supragranular and infragranular dynamics. Maier et al. (2010) found that supragranular sites had higher broadband gamma power than infragranular CHIR-99021 cell line sites. This pattern was reversed in the alpha and beta

range, with greater power in the infragranular and granular layers. Finally, the spiking activity of neurons in the superficial layers of visual cortex are more coherent with gamma-frequency oscillations in the local field potential, while neurons in deep layers are more coherent with alpha-frequency oscillations (Buffalo et al., 2011). This finding is consistent with an earlier study by Livingstone (1996) showing that 50% of cells in L2/3 of squirrel monkey V1 expressed gamma oscillations, compared to less than 20% of cells

in L4C and infragranular layers. The different spectral behavior of superficial and deep layers has led to the interesting proposal that feedforward and feedback signaling may be mediated by distinct (high and low) frequencies (reviewed in Wang, 2010; see also Buschman and Miller, 2007), a proposal that has recently received experimental support, at least for the feedforward connections (Bosman et al., 2012; see also Gregoriou et al., 2009). Given this functional and anatomical segregation into parallel streams, the question naturally arises, how are these streams integrated? It has been previously suggested that integration occurs through the synchronized firing of multiple neurons that MLN0128 purchase form a neural ensemble (Gray et al., 1989; Singer, 1999), while others have emphasized interareal phase synchronization or coherence (Varela et al., 2001; Fries, 2005; Fujisawa and Buzsáki, 2011). While a full treatment of this

question is beyond the scope of the current Perspective, we propose that the canonical microcircuit contains a clue for how the dialectic between segregation and integration might be resolved. While top-down and bottom-up inputs and outputs may be segregated in layers, streams, and frequency bands, the canonical microcircuit specifies the circuitry for how the basic units of cortex are interconnected and therefore how the intrinsic activity of the cortical column is entrained by extrinsic inputs. This intrinsic connectivity specifies how the cells of origin only and termination of extrinsic projections are interconnected and thus determines how top-down and bottom-up streams are integrated within each cortical column. The notion of a canonical microcircuit implicitly assumes that each circuit is distinct from its neighbors, which could presumably carry out computations in parallel. Therefore, the canonical microcircuit specifies the spatial scale over which processing is integrated. The most likely candidate for this spatial scale is the cortical column, which can vary over three orders of magnitude between minicolumns, columns, and hypercolumns.