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Sensorimotor decision-making in a mouse model of Rett Syndrome

About This PhD Project

Project Description

Project Code: 2020-SIDB-02

Sensorimotor decision-making is an integral part of mammalian behaviour, whereby multi-modal streams of sensory information converge to drive the selection of an appropriately timed motor response (Galinanes et al., 2018). Deficits in visuomotor decision-making is a cornerstone phenotype of many autism spectrum disorders (ASDs) (Sharer et al., 2015), but the underlying causal mechanisms remain largely unresolved.

This PhD project will explore the hypothesis that disrupted visuomotor integration in frontotemporal motor areas underpins abnormal sensorimotor decision-making in a mouse model of Rett Syndrome. The experiments will employ a novel touchscreen-based 2-alternative forced-choice (2-AFC) task for mice that can be used to assess visuomotor decision-making in head-restrained mice. By performing 2-photon population calcium imaging and/or high-density Neuropixel probe recordings in the anterior lateral motor region (ALM) – a defined frontal visuomotor area of cortex – across learning, the project will unravel the causal mechanisms underpinning visuomotor decision-making in the healthy brain and circuit defects that lead to abnormal processing in a mouse model of Rett syndrome. The project will also address whether abnormal visuomotor decision-making in Rett mice can be reversed both at the circuit and phenotypic level using viral-based delivery of the X-linked MECP2 gene in neurons (Guy et al., 2007).


1. Galiñanes GL, Bonardi C & Huber D. (2018) Directional Reaching for Water as a Cortex-Dependent Behavioral Framework for Mice. Cell Rep. 22(10):2767-2783.

2. Guy J, Gan J, Selfridge J, Cobb S, & Bird A. (2007). Reversal of neurological defects in a mouse model of Rett syndrome. Science. 315(5815):1143-7.

3. Sharer, E., Crocetti, D., Muschelli, J., Barber, A. D., Nebel, M. B., Cao, B. S., Pekar, J. J. & Mostofsky, S. H. (2015) Neural correlates of visuomotor learning in autism. Journal of Child Neurology 30(14), 1877.

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