The overall objective of the proposed research is to gain an understanding of the molecular events which underlie processes involved in learning and memory. One model used to study such processes is long-term potentiation (LTP), a type of induced plasticity where the efficacy of synapses is enhanced in a fashion similar to that which occurs during some forms of learning. Recent evidence suggests that GAP-43, an axonally transported phosphoprotein whose synthesis and transport is specifically enhanced during nerve growth and regeneration, may play an important role in LTP. Another model used to study synaptic plasticity is reactive synaptogensis, where normal axons grow and reinnervate denervated areas. In the proposed studies. quantitative electrophoretic and EM, subcellular fractionation. in vitro and in situ hybridization methods, will be used to determine if GAP-43 phosphorylation is correlated with axon growth and/or release of neurotransmitter during LTP, and if GAP-43 plays a role in the growth of axons which occurs during reactive synaptogenesis in the rat hippocampal formation. These studies promise to provide important information regarding the molecular events which occur during synaptic plasticity and may contribute to our understanding of the role played by protein phosphorylation in processes underlying learning and memory.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS025150-02
Application #
3410314
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1988-12-01
Project End
1991-11-30
Budget Start
1989-12-01
Budget End
1990-11-30
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
McAdory, B S; Van Eldik, L J; Norden, J J (1998) S100B, a neurotropic protein that modulates neuronal protein phosphorylation, is upregulated during lesion-induced collateral sprouting and reactive synaptogenesis. Brain Res 813:211-7
Lin, L H; Van Eldik, L J; Osheroff, N et al. (1994) Inhibition of protein kinase C- and casein kinase II-mediated phosphorylation of GAP-43 by S100 beta. Brain Res Mol Brain Res 25:297-304
Hess, D T; Lin, L H; Freeman, J A et al. (1994) Modification of cysteine residues within G(o) and other neuronal proteins by exposure to nitric oxide. Neuropharmacology 33:1283-92
Lin, L H; Bock, S; Carpenter, K et al. (1992) Synthesis and transport of GAP-43 in entorhinal cortex neurons and perforant pathway during lesion-induced sprouting and reactive synaptogenesis. Brain Res Mol Brain Res 14:147-53
Costello, B; Lin, L H; Meymandi, A et al. (1991) Expression of the growth- and plasticity-associated neuronal protein, GAP-43, in PC12 pheochromocytoma cells. Prog Brain Res 89:47-67
Norden, J J; Lettes, A; Costello, B et al. (1991) Possible role of GAP-43 in calcium regulation/neurotransmitter release. Ann N Y Acad Sci 627:75-93