Evidence for a Role of GluN2C/GluN2D-Containing NMDA Receptors in Neuronal Oscillations

Synchronization of neuronal firing leads to neural oscillations (brain waves) which are critical to working memory, cognition, and perception. NMDA receptors (NMDARs) play a vital role in establishing appropriate neural oscillations and modulating brain activity. Abnormalities in NMDARs have been linked to diseases such as schizophrenia causing impairments in working memory, cognition, and perception, which is thought to be due to abnormal brain wave patterns. Consistent with this hypothesis, general NMDA receptor blockers produce exaggerated neuronal oscillations and schizophrenia-like symptoms. Several NMDAR subtypes exist, and novel disease treatments may depend on targeting a select group of NMDAR subtypes. The drug UBP791 is a competitive antagonist that has a higher binding affinity for GluN2C/2D over GluN2A/2B. The selectivity of UBP791 allows for discrimination between these receptor subtypes and identifying the role of various NMDARs.https://digitalcommons.unmc.edu/surp2021/1015/thumbnail.jp