The University of Vermont & State Agricultural College (UVM) has been awarded a $207,387 Project Grant from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) federal grant program. The grant supports research aimed at understanding the neocortical and hippocampal circuit dysfunction associated with variants of the KCNT1 gene that result in intellectual disability and a range of developmental seizure disorders. UVM researchers will conduct simultaneous high-density electrophysiological characterization and optogenetic testing of activity in dentate gyrus somatostatin-positive (SST+) and parvalbumin-positive (PV+) interneuron subtypes to elucidate the role of interneuronopathy in the KCNT1 model of epilepsy. The project seeks to establish a causal link between gene-induced interneuronopathy, cell function, and circuit susceptibility to hyperexcitation, while also exploring therapeutic approaches based on selective stimulation of SST+ interneurons to rectify inhibitory function and attenuate epileptiform discharges.
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