Grant: Project Grant

The cognitive deficits of developmental disorders carry life-long personal, familial, and societal costs. Domains of cognition mediated by the prefrontal and other associative cortical regions appear especially vulnerable to disruption. Independence in education and the workplace relies on the ability to synthesize information from multiple external and internal sources in order to direct behaviour. Deficits in such integrative cognition carry a disproportionate burden of disease and have been thought to be immutable. However, recent work suggests the window of opportunity to treat cognitive symptoms remains unexpectedly open into adulthood. The proposed experiments characterize high-impact cellular mechanisms of cortical integration with respect to their vulnerability to perturbation. We focus on a subset of neurodevelopmental disorders associated with genetic disruption of one essential subtype of excitatory receptor. The properties of this receptor make it essential for the synthesis and processing of information. We use molecular, electrophysiological, and pharmacological tools - together with extensive behavioural investigation - to interrogate and quantify the impact of treatments to restore this receptor population critical for normal cognitive function.