Description: The long-range goal is to identify common mechanisms that mediate formation of new synaptic connections during development and in the mature nervous system during learning. Synaptic connections formed during development continue to be modified in post-embryonic life by various environmental stimuli. Synapses between sensory and motor neurons in adult Aplysia are modified for long duration by stimuli that produce both non-associative and associative conditioning of defensive withdrawal reflexes. These modifications include alterations in synaptic efficacy and the formation of new sensory neuron varicosities with transmitter release sites. What reciprocal cellular and molecular signals between pre- and postsynaptic neurons initiate and maintain the formation of new synaptic connections in the mature nervous system? What type of signals are required for targeting long-term structural and functional changes to cell- or branch-specific portions of neural circuits? In this proposal, a model in vitro system consisting of identified sensory and motor neurons isolated form the central ganglia of the marine mollusc Alysia californica will be studied with cellular techniques (electrophysiology, pharmacology, immunostaining and light microscopy) and molecular techniques (RT-PCR, fluorescent in-situ hybridization) to examine the following hypotheses: 1) Cell- and branch-specific changes in mRNA expression and accumulation and their local translation contribute to various forms of associative and non-associative long-term synaptic facilitation. 2) Local reciprocal interactions via cell adhesion molecules and release of peptides and growth factors contribute to plasticity at specific sites by regulating local mRNA accumulation and translation. 3) Correlated activity in specific inputs produces cell-specific long-term facilitation by selectively activating cell and molecular changes at one set of connections while suppressing critical changes at the other connections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH060387-01A2
Application #
6260478
Study Section
Special Emphasis Panel (ZRG1-IFCN-7 (01))
Program Officer
Asanuma, Chiiko
Project Start
2001-02-15
Project End
2006-01-31
Budget Start
2001-02-15
Budget End
2002-01-31
Support Year
1
Fiscal Year
2001
Total Cost
$222,229
Indirect Cost
Name
New York State Psychiatric Institute
Department
Type
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Hu, Jiangyuan; Adler, Kerry; Farah, Carole Abi et al. (2017) Cell-Specific PKM Isoforms Contribute to the Maintenance of Different Forms of Persistent Long-Term Synaptic Plasticity. J Neurosci 37:2746-2763
Hu, Jiangyuan; Ferguson, Larissa; Adler, Kerry et al. (2017) Selective Erasure of Distinct Forms of Long-Term Synaptic Plasticity Underlying Different Forms of Memory in the Same Postsynaptic Neuron. Curr Biol 27:1888-1899.e4
Hu, Jiang-Yuan; Levine, Amir; Sung, Ying-Ju et al. (2015) cJun and CREB2 in the postsynaptic neuron contribute to persistent long-term facilitation at a behaviorally relevant synapse. J Neurosci 35:386-95
Hu, Jiangyuan; Schacher, Samuel (2015) Persistent Associative Plasticity at an Identified Synapse Underlying Classical Conditioning Becomes Labile with Short-Term Homosynaptic Activation. J Neurosci 35:16159-70
Schacher, Samuel; Hu, Jiang-Yuan (2014) The less things change, the more they are different: contributions of long-term synaptic plasticity and homeostasis to memory. Learn Mem 21:128-34
Hu, Jiang-Yuan; Schacher, Samuel (2014) Persistent long-term facilitation at an identified synapse becomes labile with activation of short-term heterosynaptic plasticity. J Neurosci 34:4776-85
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
Hernández, A Iván; Wolk, Jason; Hu, Jiang-Yuan et al. (2009) Poly-(ADP-ribose) polymerase-1 is necessary for long-term facilitation in Aplysia. J Neurosci 29:9553-62
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

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