Our group is interested in how the brain controls and adapts movement. In this project, we take a disease-first approach, using human genetic disorders both as translational models and as entry points to uncover fundamental cellular and circuit mechanisms of motor control. For this purpose, we use the small and transparent larval zebrafish model, which enables comprehensive brain-wide analyses of neurological and cellular/circuit mechanisms underlying behavioural regulation, as well as high-throughput behavioural approaches for translational studies and drug screening.

Mutations in ATP1A3, which encodes the neuron-enriched α3 subunit of the Na⁺/K⁺-ATPase, cause a spectrum of rare and highly debilitating neurological disorders characterized by severe movement abnormalities (dystonia, hemiplegia, ataxia), epilepsy and cognitive impairment. Many of these symptoms are episodic, with severe attacks often triggered by physiological stressors (e.g., fever, exertion, or illness), followed by variable degrees and durations of recovery. How altered ATP1A3 function destabilizes neural circuits to produce these episodic and triggerable phenotypes remains poorly understood.

I will describe results from a collaborative project with Dr. Tod Thiele’s group (Pepperdine University, USA), documenting the behavioural and neurological phenotypes of a novel atp1a3a mutant. I will discuss the insights this work provides into potential circuit mechanisms underlying these debilitating disorders, as well as critical loci within the telencephalon involved in movement control.