Project Summary

John Norman Armstrong, Ph.D. (Young Investigator 2004) of the Salk Institute for Biological Studies, aims to study in a mouse model the relationship between spines--neuronal projections--in the pre-frontal cortex and the disorganized thought and speech characteristic of schizophrenia. Spines are thin protrusions that receive incoming information from other neurons at synapses. Neurons in the pre-frontal cortex of schizophrenics have fewer spines. Dr. Armstrong hypothesizes that decreased spine density may affect prefrontal cortex neurons from communicating effectively with other neurons. He will measure spine density and synaptic communication in a mouse that lacks a protein called EphB, which normally binds to the protein ephrin B to maintain spine number and neuronal interactivity. He expects mice lacking EphB in their prefrontal cortex might have a reduced spine density (as seen in schizophrenia) and neuronal transmission irregularities. He also will block the activity of the protein RGS, which is decreased in schizophrenia and may interact with the EphBs/Ephrins, to elucidate RGS’s role in EphB/ephrinB signaling.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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