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Chemical synapses are specialized sites of cell-cell contact designed to transmit signals between nerve cells in the brain, and between nerves and muscles in the rest of the body. All conscious and unconscious brain functions, including learning and memory formation and body movement, depend on these connections. While there has been great progress in understanding the structure and function of synapses, much less is known about their maintenance. Yet this aspect is crucial for basic brain activity, preservation of new and old memories, and retention of many motor skills learned over the course of a lifetime. Indeed, the devastating cognitive impairments in major brain disorders, such as AD (Alzheimer’s Disease), seem to involve major synaptic loss.
Cooperation Profs. Ziv and Garner set out to gain new insights into the various processes that might be responsible for synaptic "wear and tear," thereby affecting the integrity and properties of individual synaptic connections. Findings These experiments confirmed the growing notion that synapses are dynamic structures that undergo continuous assembly and disassembly. These processes were also found to be use-dependent (or accelerated by synaptic activation or “wear”). Profs. Ziv and Garner also discovered that neighboring synapses constantly interchange their molecular constituents, effectively sharing local pools of synaptic molecules. Using similar methods, they showed that replenishment rates are far slower than local dynamics, emphasizing the latter’s importance in synaptic deconstructive and reconstructive processes. These findings raise new questions about how synapses maintain their individual identities over long periods. Profs. Ziv and Garner are now doing experiments in which they eliminate hypothetical “core” synaptic molecules in order to probe the hypothesis that synapses possibly contain a small but essential set of “core” molecules, functioning as "islands of stability in a sea of change"
Photo-activation of synaptic molecules in synapses on one side of a dendritic segment (orange) is followed by migration and incorporation of the photo-activated molecules (blue) into neighboring synapses.
NEUROPROTECTIVE PEPTIDES IN HEALTH AND DISEASE
Prof. Illana Gozes: Department of Clinical Biochemistry, Tel Aviv University
"The BSF grants were excellent in fostering our collaborative work toward understanding the mechanism of action of activity-dependent neuroprotective proteins and peptides during development and aging."
Prof. Douglas E. Brenneman: Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (now at the R&D Department, Johnson and Johnson, Pennsylvania)
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Synaptic Maintenance Processes |
