Medical Student Research Fellowship for Summer 2005

Mentor: Robert W. Greene, M.D., Ph.D.
Department: Psychiatry
Room number: VA-106
Mail Code: VA-116A
Phone number: 214 857 0805
E-mail: robertw.greene@utsouthwestern.edu
Project title: Localized NMDA receptor-dependent function in cognition

Human subjects IRB approved project number (where applicable):

Animal subjects IRB approved project number (where applicable): APN: 02-109

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects): basic research

Brief Description of Project:
Numerous studies have shown that the hippocampus is involved in the pathophysiology of psychotic disorders, such as schizophrenia. Found within the hippocampus, an area critical for learning and memory--particularly of spatiotemporal context-are NMDA receptors. These receptors are important in mediating fast excitatory neurotransmission. Different substances that block NMDA receptors have been shown to produce transient psychosis in normal individuals, and exacerbate this phenomenon in schizophrenics. Hence, using sophisticated molecular techniques and novel behavioral models, these studies are to test the hypothesis that behavioral sequelae associated with psychotic disorders depend on impaired NMDA receptor function. We will be using transgenic mice bred in our laboratory. These mice have an essential gene for the NMDA receptor modified in such a way that when it is exposed to a specific enzyme (Cre) it will be deleted. Before the deletion these mice behave and thrive normally. When they are adult they will be microinjected with a non-infectious viral vector which will introduce the Cre enzyme into the hippocampus resulting in a deletion of the NMDA receptor gene that is localized to that area. The behavior of these mice will be examined before and after the microinjections. The areas of interest within the hippocampus are CA3, CA1, dentate and entorhinal cortex, where associative learning is believed to occur. The behavior tasks will involve spatial and temporal contextual memory tasks, in which correct choices are determined by the context. This will help us understand the role of NMDA receptors in discrete regions of hippocampus in different forms of cognition, which are impaired in psychotic disorders.

Previous Research Activities or Publications with Medical Students:

Bergeron, R., Meyer, T., Coyle, J.T., and Greene, R.W. Modulation of N-methyl-d-aspartate recepotor function by glycine transport. Proc. Nat. Acad. Sci. 1998; 95: 15730-15734. Med student: Torsten Meyer

Monteggia, L.M., Barot, M., Powell, C.M., Berton, O., Galanis, V., Gemelli, T., Meuth, S., Nagy, A., Greene, R.W., Nestler, E.J. Essential role of brain derived neurotrophic factor in adult hippocampal function. Proc.Nat.Acad.Sci. 2004; in Press. Med student: Sven Meuth

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