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A point mutant of GAP‐43 induces enhanced short‐term and long‐term hippocampal plasticity
Author(s) -
Hulo S.,
Alberi S.,
Laux T.,
Muller D.,
Caroni P.
Publication year - 2002
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2002.02026.x
Subject(s) - long term potentiation , synaptic plasticity , transgene , neuroscience , hippocampal formation , microbiology and biotechnology , neurotransmission , biology , phosphorylation , gap 43 protein , genetically modified mouse , chemistry , biochemistry , immunology , gene , receptor , immunohistochemistry
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.