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bioRxiv · 10.1101/2024.06.27.600928

Highly synchronized inhibition from Purkinje cells entrains cerebellar output in zebrafish

Agarwal, V.·Narayanan, S.·Sengupta, M.·Varma, A.·Sarkar, S.·Chinta, S.·Thirumalai, V.
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Abstract

Cerebellar function, known to be important for motor learning and motor coordination, is mediated by efferent neurons that project to diverse motor areas. To understand cerebellar function, it is imperative to study how these efferent neurons integrate inputs from the principal neurons of the cerebellar cortex, the inhibitory Purkinje neurons (PNs). In zebrafish, PNs are bistable and we show here that bistability influences spike synchrony among PNs. Bistability also alters spike correlation with motor bouts. We asked how PN population synchrony influences Eurydendroid cells (ECs), which are postsynaptic targets of PNs and are the cerebellar efferent cells in zebrafish. Using optogenetics, we artificially modulated population synchrony of PNs over millisecond time scales and showed that under conditions of high synchrony, EC firing is briefly suppressed and entrained by PN spiking. However, the magnitude of such modulation is relatively small and indicates a strong combined influence of other synaptic inputs on EC spiking. Key PointsO_LICerebellar Purkinje neurons (PN) in larval zebrafish alter simple spike correlations with each other based on cellular state. C_LIO_LIThey also alter simple spike correlations with motor bouts as a function of state. C_LIO_LIWe altered PN population synchrony in a graded manner using optogenetics. C_LIO_LIPN targets are cerebellar efferent neurons, which in teleosts are called eurydendroid cells. C_LIO_LIWhen PN population is firing with high synchrony, eurydendroid cells are entrained better than when the PN input is asynchronous. C_LIO_LIThis can explain how PNs use bistability to modulate their influence on cerebellar output and ultimately, motor behavior. C_LI

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Agarwal, V., Narayanan, S., Sengupta, M., Varma, A., Sarkar, S., Chinta, S., Thirumalai, V.. 2024-06-27. Highly synchronized inhibition from Purkinje cells entrains cerebellar output in zebrafish. https://doi.org/10.1101/2024.06.27.600928

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