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NIDA Proteomics Center
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Investigators
> Robert C. Malenka
Dynamic Phosphoproteomic Analysis
of Synaptic Plasticity
Robert C. Malenka, Department of Psychiatry and Behavioral Sciences,
Stanford University
Long-lasting forms of synaptic plasticity are commonly accepted as important
contributors to the neural circuit adaptations underlying all forms of
experience-dependent plasticity, including learning and memory. Importantly, it
is now widely believed that synaptic plasticity plays a role as one of the key
neural substrates underlying the development of addiction. In vivo
administration of drugs of abuse have been found to elicit or impair a variety
of forms of synaptic plasticity in a number of different brain regions including
the ventral tegmental area, nucleus accumbens, prefrontal cortex and
hippocampus. Thus understanding the core molecular processes mediating the
induction and expression of various forms of synaptic plasticity will provide
information that is critical for understanding the brain adaptations that lead
to addiction. The induction of long-term synaptic plasticity in the mammalian
brain, the proposed synaptic basis of learning and memory, depends upon the
activity of kinases and phosphatases. While activity of several protein kinases,
most importantly that of CaMKII, is associated with the induction of long-term
potentiation (LTP), our previous studies, as well as those of others, have found
that induction of long-term depression (LTD) is thought to depend upon the
action of serine/threonine phosphatases, specifically calcineurin (PP2B) and
protein phosphatase 1 (PP1). The aim of our proposed study is to characterize
the dynamics of phosphorylation events occurring during the chemical induction
of LTD in the CA1 region of the hippocampus and to identify substrate(s) of
calcineurin. This project will be performed in close collaboration with Dr.
Angus Nairn and the Post-translational Modification Core of the Yale/NIDA
Neuroproteomics Center. |
