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.
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