Project 6

The impact of NMDA receptor hypofunction on schizophrenia-relevant sensory neurophysiological function

Project 6 aims to:

• Evaluate the efficacy of a novel glycine inhibitor using EEG biomarkers of deficits in schizophrenia
• Develop rodent neurophysiological and behavioral analogs of human/primate EEG, ERP and sensory processing measures currently being studied under ongoing Conte projects
• Evaluate effects of specific pharmacological manipulations of the NMDA receptor on rodent neurophysiological and behavioral measures
• Evaluate the effects of novel NMDAR stimulation strategies on rodent neurophysiological and sensory processing analogs

This project incorporates two avenues of research. The first aims to determine the degree to which RG1678, a novel glycine transport inhibitor, reverses the oscillatory hierarchical deficits observed in schizophrenia. We are conducting frequency-domain analyses on data from the ongoing industry-funded trial of RG1678 in order to test the compound’s effect on reversal of the prestimulus theta and gamma deficits and impaired theta/delta coupling previously observed in schizophrenia.

The second research avenue implements a novel rodent preclinical project to evaluate brain mechanisms underlying neuronal oscillatory disturbances observed in schizophrenia in order to ultimately serve as a platform for preclinical drug development. This project uses complementary pharmacological and molecular biological approaches in rodent models.

Investigators: Holly Moore, PhD (Principal Investigator), Peter Lakatos, MD, PhD (Co-Investigator)