Scientific article

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

Published inEuropean journal of neuroscience, vol. 15, no. 12, p. 1976-1982
Publication date2002

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.

  • Amino Acid Sequence/genetics
  • Animals
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists/pharmacology
  • Excitatory Postsynaptic Potentials/drug effects/genetics
  • GABA Antagonists/pharmacology
  • GAP-43 Protein/ deficiency/genetics
  • Gene Expression/drug effects/physiology
  • Hippocampus/cytology/ growth & development/ metabolism
  • Long-Term Potentiation/drug effects/ genetics
  • Mice
  • Mice, Transgenic
  • Neurons/cytology/drug effects/ metabolism
  • Organ Culture Techniques
  • Phenotype
  • Phorbol 12,13-Dibutyrate/pharmacology
  • Phosphorylation
  • Point Mutation/drug effects/ genetics
  • Protein Kinase C/drug effects/metabolism
  • Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/metabolism
  • Synaptic Transmission/drug effects/genetics
  • Up-Regulation/drug effects/ genetics
Citation (ISO format)
HULO, S. et al. A point mutant of GAP-43 induces enhanced short-term and long-term hippocampal plasticity. In: European journal of neuroscience, 2002, vol. 15, n° 12, p. 1976–1982. doi: 10.1046/j.1460-9568.2002.02026.x
Updates (1)
ISSN of the journal0953-816X

Technical informations

Creation08/06/2010 1:46:44 PM
First validation08/06/2010 1:46:44 PM
Update time03/14/2023 3:58:37 PM
Status update03/14/2023 3:58:37 PM
Last indexation10/18/2023 11:02:03 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack