Project Summary

Eleonore Real, Ph.D. (Young Investigator 2006) of Cold Spring Harbor Laboratory, plans to study glutamate receptor trafficking and synaptic plasticity, as glutamate abnormalities have been implicated in psychotic disorders such as schizophrenia and depression. Ionotropic glutamate receptors (AMPA and NMDA receptors) are the major excitatory receptors in the central nervous system. Long-term potentiation is the leading cellular model of synaptic plasticity to elucidate associative forms of learning in the central nervous system. Long-term potentiation induction requires synaptic insertion of new AMPA receptors (AMPARs) containing subunits with a long C-terminal cytoplasmic tail (GluRl and GluR4). In the adult hippocampus, GluR1-containing AMPARs are driven to the synapses due to NMDAR activation. Many studies have focused on AMPAR trafficking at synapses, but little is known about the intracellular trafficking of AMPARs before they reach the synapses. Dr. Real will study the key steps of AMPAR trafficking by focusing on two protein partners of GluR1 : SAP97 and 4.1N. She will also examine the role of the phosphorylation of GluRl at Serine 845 in its trafficking. These studies will establish molecular interactions and subcellular pathways employed by receptors to reach synapses during plasticity.

Program Area: MULTIPLE FOCUS\Mood Disorders/Schizophrenia\Unipolar/Schizophrenia

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