Hyperpolarization-activated currents drive neuronal activation sequences in sleep

Sequential neuronal patterns are believed to support information processing in the cortex, yet their origin is still a matter of debate. We report that neuronal activity in the mouse postsubiculum (PoSub), where a majority of neurons are modulated by the animal's head direction, was sequentially activated along the dorsoventral axis during sleep at the transition from hyperpolarized "DOWN" to activated "UP" states, while representing a stable direction. Computational modeling suggested that these dynamics could be attributed to a spatial gradient of hyperpolarization-activated currents (I_h), which we confirmed in ex vivo slice experiments and corroborated in other cortical structures. These findings open up the possibility that varying amounts of I_h across cortical neurons could result in sequential neuronal patterns and that traveling activity upstream of the entorhinal-hippocampal circuit organizes large-scale neuronal activity supporting learning and memory during sleep.