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Title

A point mutant of GAP-43 induces enhanced short-term and long-term hippocampal plasticity

Authors
Hulo, S.
Laux, T.
Caroni, P.
Published in European Journal of Neuroscience. 2002, vol. 15, no. 12, p. 1976-1982
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.
Keywords Amino Acid Sequence/geneticsAnimalsElectric StimulationExcitatory Amino Acid Antagonists/pharmacologyExcitatory Postsynaptic Potentials/drug effects/geneticsGABA Antagonists/pharmacologyGAP-43 Protein/ deficiency/geneticsGene Expression/drug effects/physiologyHippocampus/cytology/ growth & development/ metabolismLong-Term Potentiation/drug effects/ geneticsMiceMice, TransgenicNeurons/cytology/drug effects/ metabolismOrgan Culture TechniquesPhenotypePhorbol 12,13-Dibutyrate/pharmacologyPhosphorylationPoint Mutation/drug effects/ geneticsProtein Kinase C/drug effects/metabolismReceptors, N-Methyl-D-Aspartate/antagonists & inhibitors/metabolismSynaptic Transmission/drug effects/geneticsUp-Regulation/drug effects/ genetics
Stable URL http://archive-ouverte.unige.ch/unige:10301
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PMID: 12099903
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