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 head-direction cortex (HDC, i.e., the post-subiculum) was sequentially activated along the dorso-ventral axis during sleep at the transition from hyperpolarized “DOWN” to activated “UP” states, while representing a stable direction. Computational modelling suggested that these dynamics could be attributed to a spatial gradient of hyperpolarization-activated current (Ih), which we confirmed in ex vivo slice experiments and corroborated in other cortical structures. These findings open up the possibility that varying amounts of Ih across cortical neurons could result in sequential neuronal patterns, and that travelling activity upstream of the entorhinal-hippocampal circuit organises large-scale neuronal activity supporting learning and memory during sleep. Highlights ### Competing Interest Statement The authors have declared no competing interest.