Project Summary

Haining Zhong, Ph.D. (Young Investigator 2005) of Cold Spring Harbor Laboratory, proposes using a novel fluorescence and microscopy technique to study the activity of the cAMP/protein kinase pathway in living neurons to understand its role in synaptic plasticity, which may be altered in schizophrenia. The cAMP/protein kinase A (PKA) pathway is important because it is required for many forms of synaptic plasticity and gene regulation. However, the dynamics of this pathway in synaptic plasticity are still unknown, partly because the signaling events, transient and restricted within small synaptic compartments, are inaccessible to conventional biochemical or electrophysiological techniques. To overcome this difficulty, Dr. Zhong has developed a technique based on two-photon microscopy that can perform quantitative, high-resolution measurements of FRET (fluorescence resonance energy transfer) even in light-scattering brain slices. FRET, which indicates the distance between two fluorophores, is the basis of several genetically-encoded sensors for cAMP/PKA signaling. These sensors and the FRET-measuring technique will allow quantitative measurements of c AMP/PKA activity in living neurons with high spatial and temporal resolution. Dr. Zhong expects to introduce sensors into neurons in hippocampal slices and to monitor the activity of the cAMP/PKA pathway in small synaptic compartments in the context of synaptic plasticity. This study should deepen understanding of cAMP/PKA signaling in hippocampal synaptic plasticity, and in turn, facilitate the study of neuropathology in schizophrenia.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia\Molecular

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