Project Grant R01NS148198

This Project Grant, awarded May 7, 2026, by the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853), provides $473,860 in federal funding to The Regents of the University of Colorado-Denver through February 28, 2031. The award supports basic neuroscience research investigating heterosynaptic mechanisms that drive elevated synaptic inhibition and impaired synaptic plasticity following cardiac arrest-induced global cerebral ischemia. The research employs an in vivo rodent model of cardiac arrest to examine how GABAergic (inhibitory) synapses are strengthened in surviving neurons through postsynaptic clustering of GABAA receptors and associated scaffold proteins, with the hypothesis that this upscaling of inhibitory synapses is maladaptive and contributes to impaired excitatory synaptic transmission and cognitive dysfunction.

The project will deliver research outputs through integrated electrophysiology, imaging, and biochemical analyses to evaluate changes in inhibitory and excitatory synapse structure and function following ischemia. The investigators will employ pharmacological, genetic, and optogenetic manipulations to target synaptic receptors and intracellular signaling pathways, including CaMKII-mediated mechanisms, to elucidate the fundamental mechanisms underlying cognitive impairments associated with cardiac arrest. This research directly supports NINDS's mission to reduce the burden of neurological disease by advancing understanding of brain and nervous system function and developing knowledge applicable to post-cardiac arrest cognitive recovery.