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A Mechanism for Extinction of Classically Conditioned Forelimb Movement in Mice

Abstract

The cerebellum has long been hypothesized to be involved in the storage and expression of motor memories. Work presented in this thesis demonstrates that optogenetically conditioned motor memories are stored in the cortical and nuclear regions of the cerebellum and expressed via disinhibition-mediated bursting of the cerebellar nuclei. Building on this observation we sought to determine the impact of preventing disinhibition of the cerebellar nuclei when cueing an optogenetically conditioned forelimb movement. By transiently increasing inhibition of cerebellar nuclei during high-speed video recordings of mice responding to a previously conditioned auditory cue, we demonstrated that preventing disinhibition of cerebellar nuclei prevents the expression of the learned forelimb movements. We conclude that disinhibition-mediated bursting of the cerebellar nuclei is necessary for retrieving the motor memory and the subsequent forelimb movement. Furthermore, this mechanism could be relevant for the expression of other kinds of motor memories.

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