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.