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 (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 travelling activity upstream of the entorhinal-hippocampal circuit organises large-scale neuronal activity supporting learning and memory during sleep. Highlights Neuronal Activation Sequence in HDC : neuronal activity was sequentially reinstated along the dorsoventral axis of the HDC at UP state but not DOWN state onset. Role of I h in Sequence Generation : Incorporating the hyperpolarization-activated current (I h ) into computational models, we identified its pivotal role in UP/DOWN dynamics and neuronal activity sequences. Ex Vivo Verification : slice physiology revealed a dorsoventral gradient of Ih in the HDC. Implications Beyond HDC : the gradient of I h could account for the sequential organization of neuronal activity across various cortical areas.