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bioRxiv · 10.1101/2025.03.31.646261

Purkinje cell branch morphology determines effect of inhibition and SK2 modulation on somatic pauses

Chou, P.-J.·De Schutter, E.·Cirtala, G.
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Abstract

Characterized by a highly complex branching of their dendrites, Purkinje cells (PCs) have a unique architecture that enables them to receive impressive amounts of sensorimotor information through their parallel fiber (PF) input. They are tasked to encode this information with high accuracy. In this work, we discuss the mechanisms through which PCs encode this information, and we show how they multiplex between linear-rate and burst-pause coding. Particularly, somatic pauses are of utmost importance due to their involvement in learning. Using a novel heterogeneous model, we show that all branches can achieve a burst-pause response in response to branch-specific PF clustered input. We quantify the somatic pauses obtained and propose various mechanisms to alter the pause duration. Firstly, our results show that increasing local SK2 channel conductance density systematically increases pause duration. In four branches somatic pauses occurred only when SK2 conductance was increased. Interestingly, when adding feed-forward inhibition via stellate cells, our results show either an increase or a decrease in somatic pauses, highlighting the important role of branch morphology and branch location within the PC. Significance statementPurkinje cells are characterized by highly intricate dendritic branches, which enables them to encode sensorimotor information with great accuracy. Their somatic pauses following excitatory input have been shown to have a strong impact in learning. However, little is known about the impact of morphology and inhibitory input on somatic pauses and implicitly on the learning capacity. In this study, we propose a heterogeneous Purkinje cell model which highlights the importance of branch-specific dendritic morphology on somatic responses. We uncover two different mechanisms for modulating the length of the somatic pauses: density of SK2 channels and feed-forward inhibition via stellate cells.

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Chou, P.-J., De Schutter, E., Cirtala, G.. 2025-04-04. Purkinje cell branch morphology determines effect of inhibition and SK2 modulation on somatic pauses. https://doi.org/10.1101/2025.03.31.646261

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