The brain's complex functions are enabled through the interactions of networks of neurons that form to participate in a wide range of processes. This dynamic coordination is reflected as oscillatory fluctuations in population activity. %The brain dynamically forms networks of neurons that engage in different cognitive tasks, reflected as oscillatory fluctuations in population activity. Despite significant progress in understanding the functional and structural relations of these coordinated neurons, many underlying principles remain elusive. A comprehensive framework to understand how these microcircuits operate necessitates identifying the electrophysiological properties of constituent cell types and their connectivity. The importance of this task is especially pronounced in the context of the human brain, where the differences from animal models become more apparent, and the challenges associated with direct investigation.

In this study, we used multi-electrode arrays to record from slices of human cortical tissue obtained during epilepsy surgery. These tissue samples are not directly involved in generating seizures, providing a unique opportunity to study the isolated cortical circuitry and gain empirical evidence of the brain's intrinsic dynamics. Moreover, the in-vitro protocol allowed to capture the anatomical location of individual neurons on the brain slice. We acquired simultaneous recordings from all layers and across several columns at high temporal resolutions to extract single unit activity. The characterization of cell types and their connectivity was based on extracellular spike waveform features, temporal organization of the spikes, and their laminar identity. Glutamatergic and cholinergic agonists were introduced to the extracellular medium to stimulate coordinated neuronal activity.

Our results demonstrated heterogeneous correlation strengths amongst electrophysiologically identified pyramidal cells and interneurons (broad spiking and narrow spiking) in all cortical layers. We found that the spatial range of the strong coordinated activity is not limited to pairs with direct (mono-synaptic) connections. Additionally, we showed that when cholinergic drive induces oscillations, it modifies cortical microcircuits and reorganizes inter- and intra-laminar correlations. Specifically, while the heterogeneity in correlations (weak and strong) is preserved, the strong correlations reach longer lengths for neuron pairs in different layers (inter-layer) compared to pairs in the same layer (intra-layer) during oscillations. In other words, more neuron pairs across layers synchronize than those within layers. These findings provide insights that may help bridge the understanding of how cellular-level processes give rise to complex cognitive behaviors.