M-current modulation of cortical slow oscillations: Network dynamics and computational modeling

The slow oscillation is a synchronized network activity expressed by the cortical network in slow wave sleep and under anesthesia. Waking up requires a transition from this synchronized brain state to a desynchronized one. Cholinergic innervation is critical for the transition from slow-wave-sleep to wakefulness, and muscarinic action is largely exerted through the muscarinic-sensitive potassium current (M-current) block. We investigated the dynamical impact of blocking the M-current on slow oscillations, both in cortical slices and in a cortical network computational model. Blocking M-current resulted in an elongation of Up states (by four times) and in a significant firing rate increase, reflecting an increased network excitability, albeit no epileptiform discharges occurred. These effects were replicated in a biophysical cortical model, where a parametric reduction of the M-current resulted in a progressive elongation of Up states and firing rate. All neurons, and not only those modeled with M-current, increased their firing rates due to network recurrency. Further increases in excitability induced even longer Up states, approaching the microarousals described in the transition towards wakefulness. Our results bridge an ionic current with network modulation, providing a mechanistic insight into network dynamics of awakening.