Increasing evidence has emerged supporting the idea that many more CNS synapses are made than are eventually retained, and that this phenomenon includes a process of synapse specification in which certain sites become stabilized and others are lost. Although recent work supports that young synapses are structurally and functionally distinct, the processes by which young synapses get stabilized largely remain unknown. Protein synthesis is required for mechanisms of synaptic plasticity such as long-term potentiation (LTP) or depression (LTD), as well as for learning and memory, where synapses are likely to be structurally modified. However, it is not yet known whether the stabilization of newly formed synapses requires protein synthesis. The overall hypothesis of this proposal is that newly formed synapses are labile structures that require protein synthesis for their stabilization and subsequent maintenance. Treatments that stabilize synapses should render them more resistant to such a requirement than those that destabilize synapses. Ribosomal clustering beneath synapses has been shown to be particularly prominent during development when the capacity for protein synthesis in dendritically enriched neuropil peaks;a general requirement for protein synthesis may thus operate locally. An understanding of the regulation of synaptogenesis and of the differences between dendritic and somatic regulation of protein synthesis has great clinical significance. This link is particularly clear in Fragile X mental retardation where changes in the regulation of dendritic protein synthesis have lasting consequences on synapse morphology and plasticity

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30NS056610-04
Application #
7792240
Study Section
Special Emphasis Panel (ZNS1-SRB-M (39))
Program Officer
Talley, Edmund M
Project Start
2007-03-01
Project End
2010-06-30
Budget Start
2010-03-01
Budget End
2010-06-30
Support Year
4
Fiscal Year
2010
Total Cost
$15,004
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Sebeo, Joseph; Hsiao, Kuangfu; Bozdagi, Ozlem et al. (2009) Requirement for protein synthesis at developing synapses. J Neurosci 29:9778-93