This Project Grant award of $429,000 from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) supports research to understand the cellular and synaptic mechanisms underlying cognitive disabilities in Down syndrome.
The award to the University of Colorado-Denver will utilize a novel combination of two-photon microscopy, electrophysiology, chemogenetics, and pharmacological manipulation to examine structural and functional alterations of inhibitory and excitatory synapses in the prefrontal cortex of a Down syndrome mouse model. The research aims to determine how decreased inhibitory neuronal activity weakens GABAergic synapses and induces abnormal excitatory synapse maturation, with the goal of elucidating the pathophysiological mechanisms underlying cognitive deficits in Down syndrome. Results from this exploratory study are expected to provide new insights into how GABA signaling regulates brain development and function, with relevance to understanding and potentially treating intellectual disability in Down syndrome.
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