The formation of central synapses between appropriate partners requires local signals to allow some synaptic contacts to develop into stable synapses independently of others. This might be facilitated by local protein synthesis at synaptic endings; a process that contributes to activity-dependent changes in synaptic efficacy in the adult CNS. In this application we will test the hypothesis that appropriate cell-cell interactions target local acquisition of protein synthesis capabilities at developing synapses that contribute to the formation and long-term maintenance of synapses. Using cellular methods (electrophysiology, pharmacology, immunostaining and light and electron microscopy) and molecular techniques (RT-PCR, in situ hybridization and anti-sense methods), we plan to use a model cell culture system containing identified neurons of the marine mollusk Aplysia to examine the following aims:
Aim 1 : To determine whether local translation of exported mRNAs contribute to the formation of branch- and target-specific synapses. A) Does interaction with specific targets affect branch-specific distribution of exported mRNAs that encode molecules known to be critical for transmitter release? B) Are transported mRNAs translated at synaptic sites? C) Is local translation of mRNAs critical for the formation of synapses? Aim 2: To determine the role of intercellular signals in regulating local protein synthesis contributing to branch- and target-specific synapse formation. A) Are mRNA export and local protein synthesis regulated by expression and distribution of a cell adhesion molecule? B) Are mRNA export and local protein synthesis regulated by expression and release of secretory products, such as presynaptic neuropeptides or potential neurotrophic factors? Aim 3: To determine whether local protein synthesis is regulated by electrical activity that modulates synapse formation by competing inputs converging on a single target. A) Does asymmetric activity regulate targeting and distribution of mRNAs at active and inactive synaptic sites? B) Does asymmetric activity regulate local protein synthesis at active and inactive synaptic sites? The results of these studies will provide important information about how local interactions between neurons influence the development of behaviorally relevant neural Circuits and their specific connections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS042159-01A1
Application #
6469901
Study Section
Molecular, Cellular and Developmental Neurosciences 2 (MDCN)
Program Officer
Talley, Edmund M
Project Start
2002-04-01
Project End
2006-03-31
Budget Start
2002-04-01
Budget End
2003-03-31
Support Year
1
Fiscal Year
2002
Total Cost
$271,819
Indirect Cost
Name
Columbia University (N.Y.)
Department
Neurosciences
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Hu, Jiang-Yuan; Baussi, Orit; Levine, Amir et al. (2011) Persistent long-term synaptic plasticity requires activation of a new signaling pathway by additional stimuli. J Neurosci 31:8841-50
Hu, Jiang-Yuan; Chen, Yang; Bougie, Joanna K et al. (2010) Aplysia cell adhesion molecule and a novel protein kinase C activity in the postsynaptic neuron are required for presynaptic growth and initial formation of specific synapses. J Neurosci 30:8353-66
Hu, Jiang-Yuan; Chen, Yang; Schacher, Samuel (2007) Multifunctional role of protein kinase C in regulating the formation and maturation of specific synapses. J Neurosci 27:11712-24
Hu, Jiang-Yuan; Chen, Yang; Schacher, Samuel (2007) Protein kinase C regulates local synthesis and secretion of a neuropeptide required for activity-dependent long-term synaptic plasticity. J Neurosci 27:8927-39
Hu, Jiang-Yuan; Wu, Fang; Schacher, Samuel (2006) Two signaling pathways regulate the expression and secretion of a neuropeptide required for long-term facilitation in Aplysia. J Neurosci 26:1026-35
Sung, Ying-Ju; Wu, Fang; Schacher, Samuel et al. (2006) Synaptogenesis regulates axotomy-induced activation of c-Jun-activator protein-1 transcription. J Neurosci 26:6439-49
Hu, Jiang-Yuan; Goldman, Jonathan; Wu, Fang et al. (2004) Target-dependent release of a presynaptic neuropeptide regulates the formation and maturation of specific synapses in Aplysia. J Neurosci 24:9933-43
Hu, Jiang-Yuan; Glickman, Leonard; Wu, Fang et al. (2004) Serotonin regulates the secretion and autocrine action of a neuropeptide to activate MAPK required for long-term facilitation in Aplysia. Neuron 43:373-85
Hu, Jiang-Yuan; Meng, Xu; Schacher, Samuel (2003) Redistribution of syntaxin mRNA in neuronal cell bodies regulates protein expression and transport during synapse formation and long-term synaptic plasticity. J Neurosci 23:1804-15