Sunday, May 5, 2024
5/5/2024
PROJECT SUMMARY Spinocerebellar ataxias (SCAs) are progressive, debilitating and fatally inherited neurodegenerative diseases. Most cerebellar ataxias result from the unstable expansions of CAG repeats. Spinocerebellar ataxia type 1 (SCA1) is an inherited neurological disorder (autosomal dominant, repeat expansion) that affects the brainstem, spinocerebellar tracts and particularly the Purkinje cells in the cerebellar cortex. Currently, there are no therapies available to target disease progression. Our goal is to understand the link between brain structure, e.g., the cerebello-thalamo-cortical circuitry (CTC), brain function and gait performance in SCA1. In this proposal, we begin with querying single-unit spiking activity and local field potentials simultaneously from CTC areas and electrically neuromodulate each area in awake behaving mice transgenic models of SCA1. To do so, we will interrogate the CTC circuit in two different mice models of SCA1 in aim 1 and neuromodulate the CTC circuit in these animals to improve or aggravate gait function in aim 2. Altogether, we hypothesize that monitoring single-unit spiking activity and local field potentials simultaneously from cerebello-thalamo-cortical (CTC) areas and electrically neuromodulating each area in SCA1 awake behaving mice will reveal the neurophysiological underpinnings of SCA1 gait ataxia. Ultimately, findings from this innovative and novel study will pave the way for applying neuromodulatory therapies to SCAs.
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