The Woodin Lab studies inhibitory synaptic transmission and plasticity in the central nervous system. We are actively identifying mechanisms regulating inhibition and determining the contribution of excitation/inhibition imbalances to pathological disorders. Using a combinatorial approach that includes electrophysiology, opto- and chemogenetics, biochemistry, proteomics, imaging, and behavioural testing the Woodin Lab is currently investigating the following:
Inhibitory Synaptic Plasticity – functional significance and underlying mechanisms
Despite the well accepted role of excitatory glutamatergic synaptic plasticity in learning and memory our understanding of both the functional significance of inhibitory synaptic plasticity and the underlying mechanisms are rudimentary. The Woodin Lab is currently characterizing the spike-timing dependent plasticity of GABAergic synapses in the cortex while also determining the underlying mechanisms that regulate this process. This work focuses on the Ca-dependent regulation of the potassium-chloride co-transporter KCC2. Using mass-spectrometry we recently discovered the KCC2 interactome, revealing numerous previously unidentified KCC2 protein interactors. Through collaboration we are establishing a high-throughput method for screening putative inhibitors of KCC2-protein interaction with the ultimate goal of identifying KCC2 enhancers that strengthen inhibition.
Restoring Inhibition in Neurological Disorders and Neurodegenerative Diseases:
Amyotrophic Lateral Sclerosis (ALS), Huntington Disease (HD), and Autism Spectrum Disorders (ASD)
Reduced KCC2 expression and/or reduced synaptic inhibition is is observed in many neurological disorders and neurodegenerative diseases. The Woodin Lab uses animal models of ALS, HD, and ASD to determine efficient strategies to re-establish KCC2 function and/or restore synaptic inhibition. These strategies include gene replacement, pharmacological treatments, and the regulation of neuronal activity using optogenetic and chemogenetic strategies.