This project will examine the hypothesis that NMDA receptor hypofunction within hippocampal regions modelcentral features of the cognitive symptoms of schizophrenia. Neuropsychological studies in schizophrenicpatients have identified a core deficit in episodic memory and studies on animals strongly suggest anessential role for NMDA receptors in the hippocampus is the storage and recall of associations that underlieour capacity for episodic memory. The proposed studies will combine our own recent development of anovel protocol for the assessment of specific features of episodic memory in animals and a novel techniquefor spatially and temporally selective NMDA receptor knockout developed in Robert Greene's laboratory. Incollaborative studies we will explore the role of NMDA receptors in specific components of the hippocampalcircuit. We expect to dissociate a critical role for NMDA receptors in area CA3 in the association of stimuliand their context from a critical role for NMDA receptors in area CA1 in memory for sequential events. Wealso expect to dissociate a critical role for CA3 and CA1 NMDA receptors in 'all-or-none' episodic memoryretrieval from a crucial role for NMDA receptors in the perirhinal and entorhinal cortex in recognition basedon a sense of familiarity. Finally, we expect to identify a selective role for CA3 NMDA receptors in the linkingof related memories supporting inferences from memory. These findings will provide insights about thefunctional circuitry of hippocampal NMDA receptors, of strong relevance to other center projects that employfunctional imaging, molecular and cellular biology, and computational modeling.
Showing the most recent 10 out of 128 publications
