Project Grant R01NS143180

This Project Grant award of $496,279 was obligated on March 1, 2026, by the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853). Colorado State University's Sponsored Programs Division will conduct fundamental research to elucidate the molecular mechanisms underlying cholinergic synaptic homeostasis—the ability of neurons to compensate for altered neural activity—through the completion date of November 30, 2030. This research employs Drosophila as a genetically tractable model system to validate cholinergic homeostatic synaptic plasticity (HSP) in intact neural circuitry and to investigate the specific roles of the ER protein NACHO, transcription factors NFAT and CREB, and downstream ion channel genes in regulating this process.

The research deliverables will contribute scientific knowledge regarding cholinergic nervous system plasticity mechanisms, with findings expected to inform understanding of comparable processes in mammalian systems and potentially yield therapeutic applications for neurological conditions such as Alzheimer's disease. By characterizing highly conserved ion channel and cellular regulatory mechanisms in the fruit fly central nervous system, this investigation addresses a significant gap in synaptic plasticity research, which has historically focused on glutamatergic rather than cholinergic synapses, thereby advancing the NINDS mission to reduce the burden of neurological disease through fundamental neuroscience investigation.