Principal Investigator: Dr. Jeff Smith, Biologya
The broad objectives of this proposed research are to characterize the inhibition of GluN2B subunit-containing NMDA receptors in mouse brain by the cannabinoid Dexanabinol (HU-211) and to demonstrate its relevance for modulating NMDA receptor-dependent learning and memory in mice at both the electrophysiological and behavioral levels.
The specific aims are to: 1) Characterize inhibitory effects of HU-211 on the function of NMDA receptors in mouse brain slices using whole-cell patch clamp electrophysiology; 2) To evaluate the extent to which GluN2B-containing NMDA receptors are selectively targeted by HU-211 in mouse brain slices using whole-cell patch clamp electrophysiology; 3) to determine whether long-term potentiation is affected by HU-211 in mouse brain slices using field potential recording; and 4) To determine whether NMDA receptor dependent learning and memory in live mice is affected by administration of HU-211 during automated fear learning and memory experiments.
The proposed work is significant because it provides missing knowledge needed to advance the effective implementation of HU-211 as a selective therapeutic for brain disorders involving impaired learning and memory including depression, post-traumatic stress disorder (PTSD), stroke, brain injury, and dementia such as Huntington’s and Alzheimer’s diseases. The work is also important because it will support the education of two graduate and two undergraduate students in the neuroscience lab at CSU-Pueblo. The proposed work is also important because it will promote the establishment of a new and meaningful collaboration between the Principal Investigator and a notable neuroscientist at the University of Montana.