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bioRxiv · 10.1101/2023.09.12.557442

Hyperpolarization-Activated Currents Drive Neuronal Activation Sequences in Sleep

Mehrotra, D.·Levenstein, D.·Duszkiewicz, A. J.·Carrasco, S. S.·Booker, S. A.·Kwiatkowska, A.·Peyrache, A.
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Abstract

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. HighlightsO_LINeuronal Activation Sequence in HDC: neuronal activity was sequentially reinstated along the dorsoventral axis of the HDC at UP state but not DOWN state onset. C_LIO_LIRole of Ih in Sequence Generation: Incorporating the hyperpolarization-activated current (Ih) into computational models, we identified its pivotal role in UP/DOWN dynamics and neuronal activity sequences. C_LIO_LIEx Vivo Verification: slice physiology revealed a dorsoventral gradient of Ih in the HDC. C_LIO_LIImplications Beyond HDC: the gradient of Ih could account for the sequential organization of neuronal activity across various cortical areas. C_LI

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Mehrotra, D., Levenstein, D., Duszkiewicz, A. J., Carrasco, S. S., Booker, S. A., Kwiatkowska, A., Peyrache, A.. 2023-09-13. Hyperpolarization-Activated Currents Drive Neuronal Activation Sequences in Sleep. https://doi.org/10.1101/2023.09.12.557442

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