Our long-term goal is to define the electrophysiological, morphological and biochemical correlates of synapes formation. Most experiments are performed with cultures of cells dissociated from embryonic chick spinal cords ciliary ganglia, sensory ganglia and muscle. In nerve-muscle co-cultures, patch-clamp microelectrodes will be used to describe parameters of acetylcholine (ACh) release from growth cones and newly formed synapes, and also to monitor the accumulation of ACh receptors and acetylcholinesterase (AChE) in the postsynaptic complex. Reverse-phase HPLC and other chromatographic techniques will be used to purify factors from neural tissue that induce the synthesis of ACh receptors and AChE. Antibodies raised against purified material will be used to localize the activity and to study its role in normal development. the influence of competing neurons and of impulse activity on the stability of synapses will be studied in a new microculture system. In spinal cord-sensory neuron co-cultures, the specificity and function of synapses formed on identified motoneurons (labeled in vivo with a fluorescent probe via retrograde axonal transport) will be tested. Patch-clamp techniques will be used to assay transmitter condidates, to map the distribution of chemoreceptors, and to analyze the inonic basis of presynaptic and postsynaptic inhibition. Information about the function, stability and specificity of newly formed synapses has import for developmental neurological defects, for neural mechanisms that underlie learning and memory, and for mechanisms of degeneration and regeneration in the mature brain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS018458-09
Application #
3398501
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1981-09-01
Project End
1991-04-30
Budget Start
1989-05-01
Budget End
1990-04-30
Support Year
9
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Bianchetta, Michael J; Betensky, Rebecca A; Cohen, Jonathan B (2005) Cell-surface MuSK self-association: a crucial role for the putative signal sequence. Biochemistry 44:16229-38
Trinidad, Jonathan C; Cohen, Jonathan B (2004) Neuregulin inhibits acetylcholine receptor aggregation in myotubes. J Biol Chem 279:31622-8
Ford, Byron D; Liu, Yun; Mann, Mary Anne et al. (2003) Neuregulin-1 suppresses muscarinic receptor expression and acetylcholine-activated muscarinic K+ channels in cardiac myocytes. Biochem Biophys Res Commun 308:23-8
Ford, Byron D; Han, Bomie; Fischbach, Gerald D (2003) Differentiation-dependent regulation of skeletal myogenesis by neuregulin-1. Biochem Biophys Res Commun 306:276-81
Loeb, Jeffrey A; Hmadcha, Abdelkrim; Fischbach, Gerald D et al. (2002) Neuregulin expression at neuromuscular synapses is modulated by synaptic activity and neurotrophic factors. J Neurosci 22:2206-14
Ramarao, M K; Bianchetta, M J; Lanken, J et al. (2001) Role of rapsyn tetratricopeptide repeat and coiled-coil domains in self-association and nicotinic acetylcholine receptor clustering. J Biol Chem 276:7475-83
Viehover, A; Miller, R H; Park, S K et al. (2001) Neuregulin: an oligodendrocyte growth factor absent in active multiple sclerosis lesions. Dev Neurosci 23:377-86
Bartoli, M; Ramarao, M K; Cohen, J B (2001) Interactions of the rapsyn RING-H2 domain with dystroglycan. J Biol Chem 276:24911-7
Vartanian, T; Goodearl, A; Lefebvre, S et al. (2000) Neuregulin induces the rapid association of focal adhesion kinase with the erbB2-erbB3 receptor complex in schwann cells. Biochem Biophys Res Commun 271:414-7
Trinidad, J C; Fischbach, G D; Cohen, J B (2000) The Agrin/MuSK signaling pathway is spatially segregated from the neuregulin/ErbB receptor signaling pathway at the neuromuscular junction. J Neurosci 20:8762-70

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