Hyperpolarization-Activated Currents Drive Neuronal Activation Sequences in Sleep

Abstract

AbstractSequential 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 inex vivoslice experiments and corroborated in other cortical structures. These findings open up the possibility that varying amounts of Ihacross 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.HighlightsNeuronal 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 Ihin Sequence Generation: Incorporating the hyperpolarization-activated current (Ih) into computational models, we identified its pivotal role in UP/DOWN dynamics and neuronal activity sequences.Ex VivoVerification: slice physiology revealed a dorsoventral gradient of Ih in the HDC.Implications Beyond HDC: the gradient of Ihcould account for the sequential organization of neuronal activity across various cortical areas.