In contrast to the long-standing notion that the role of individual neurons in population activity is vanishingly small, recent studies have shown that electrical activation of only a single cortical neuron can have measurable effects on global brain state, movement, and perception. Although highly important for understanding how neuronal activity in cortex is orchestrated, the cellular and network mechanisms underlying this phenomenon are unresolved. Here, we first briefly review the current state of knowledge regarding the phenomenon of single-cell induced network modulation and discuss possible underpinnings. Secondly, we show proof of principle for an experimental approach to elucidate the mechanisms of single-cell induced changes in cortical activity. The setup allows simultaneous recordings of the spiking activity of multiple neurons across all layers of the cortex using a multi-electrode array, while manipulating the activity of one individual neuron in close proximity to the array. We demonstrate that single cells can be recorded and stimulated reliably for hundreds of trials, conferring high statistical power even for expectedly small effects of single-neuron spiking on network activity. Preliminary results suggest that single-cell stimulation on average decreases the firing rate of local network units. We expect that characterization of the spatiotemporal spread of single-cell evoked activity across layers and columns will yield novel insights into intracortical processing.