Brain orchestra under spontaneous conditions: Identifying communication modules from the functional architecture of area V1

Abstract

We used two-photon imaging to record from granular and supragranular layers in mouse primary visual cortex (V1) under spontaneous conditions and applied an extension of the spike time tiling coefficient (STTC; introduced by Cutts and Eglen) to map functional connectivity architecture within and across layers. We made several observations: Approximately, 19-34% of neuronal pairs within 300µm of each other exhibit statistically significant functional connections, compared to 10% at distances of 1mm or more. As expected, neuronal pairs with similar tuning functions exhibit a significant, though relatively small, increase in the fraction of functional inter-neuronal correlations. In contrast, internal state as reflected by pupillary diameter or aggregate neuronal activity appears to play a much stronger role in determining inter-neuronal correlation distributions and topography. Overall, inter-neuronal correlations appear to be slightly more prominent in layer 4. The first-order functionally connected (i.e., direct) neighbors of neurons determine the hub structure of the V1 microcircuit. Layer 4 exhibits a nearly flat degree of connectivity distribution, extending to higher values than seen in supragranular layers, whose distribution drops exponentially. In all layers, functional connectivity exhibits small-world characteristics and network robustness. The probability of firing of layer 2/3 pyramidal neurons can be predicted as a function of the aggregate activity in their first-order functionally connected partners within layer 4, which represent their putative input group. The functional form of this prediction conforms well to a ReLU function, reaching up to firing probability one in some neurons. Interestingly, the properties of layer 2/3 pyramidal neurons differ based on the size of their layer 4 functional connectivity group. Specifically, layer 2/3 neurons with small layer-4 degrees of connectivity appear to be more sensitive to the firing of their layer 4 functional connectivity partners, suggesting they may be more effective at transmitting synchronous activity downstream from layer 4. They also appear to fire largely independently from each other, compared to neurons with high layer-4 degrees of connectivity, and are less modulated by changes in pupil size and aggregate population dynamics. Information transmission is best viewed as occurring from neuronal ensembles in layer 4 to neuronal ensembles in layer 2/3. Under spontaneous conditions, we were able to identify such candidate neuronal ensembles, which exhibit high sensitivity, precision, and specificity for L4 to L2/3 information transmission. In sum, functional connectivity analysis under spontaneous activity conditions reveals a modular neuronal ensemble architecture within and across granular and supragranular layers of mouse primary visual cortex. Furthermore, modules with different degrees of connectivity appear to obey different rules of engagement and communication across the V1 columnar circuit.