A point mutant of GAP-43 induces enhanced short-term and long-term hippocampal plasticity.
Eur J Neurosci
; 15(12): 1976-82, 2002 Jun.
Article
em En
| MEDLINE
| ID: mdl-12099903
ABSTRACT
The growth-associated protein GAP-43 (or neuromodulin or B-50) plays a critical role during development in mechanisms of axonal growth and formation of synaptic networks. At later times, GAP-43 has also been implicated in the regulation of synaptic transmission and properties of plasticity such as long-term potentiation. In a molecular approach, we have analyzed transgenic mice overexpressing different mutated forms of GAP-43 or deficient in GAP-43 to investigate the role of the molecule in short-term and long-term plasticity. We report that overexpression of a mutated form of GAP-43 that mimics constitutively phosphorylated GAP-43 results in an enhancement of long-term potentiation in CA1 hippocampal slices. This effect is specific, because LTP was affected neither in transgenic mice overexpressing mutated forms of non-phosphorylatable GAP-43 nor in GAP-43 deficient mice. The increased LTP observed in transgenic mice expressing a constitutively phosphorylated GAP-43 was associated with an increased paired-pulse facilitation as well as an increased summation of responses during high frequency bursts. These results indicate that, while GAP-43 is not necessary for LTP induction, its phosphorylation may regulate presynaptic properties, thereby affecting synaptic plasticity and the induction of LTP.
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Base de dados:
MEDLINE
Assunto principal:
Regulação para Cima
/
Mutação Puntual
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Potenciação de Longa Duração
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Proteína GAP-43
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Hipocampo
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Neurônios
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article