Neuronal-spiking-based closed-loop stimulation during cortical ON- and OFF-states in freely moving mice.

The slow oscillation is a central neuronal dynamic during sleep, and is generated by alternating periods of high and low neuronal activity (ON- and OFF-states). Mounting evidence causally links the slow oscillation to sleep's functions, and it has recently become possible to manipulate the slow oscillation non-invasively and phase-specifically. These developments represent promising clinical avenues, but they also highlight the importance of improving our understanding of how ON/OFF-states affect incoming stimuli and what role they play in neuronal plasticity. Most studies using closed-loop stimulation rely on the electroencephalogram and local field potential signals, which reflect neuronal ON- and OFF-states only indirectly. Here we develop an online detection algorithm based on spiking activity recorded from laminar arrays in mouse motor cortex. We find that online detection of ON- and OFF-states reflects specific phases of spontaneous local field potential slow oscillation. Our neuronal-spiking-based closed-loop procedure offers a novel opportunity for testing the functional role of slow oscillation in sleep-related restorative processes and neural plasticity.