Analysis of the presynaptic signaling mechanisms underlying the inhibition of LTP in rat dentate gyrus by the tyrosine kinase inhibitor, genistein

M. Casey, C. Maguire, Á Kelly, M. A. Gooney, M. A. Lynch

Research output: Contribution to journalReview articlepeer-review

20 Citations (Scopus)

Abstract

A great deal of recent evidence points to a role for tyrosine kinase in expression of LTP. Data have been presented that are consistent with the idea that tyrosine phosphorylation of proteins occurs in both the presynaptic and postsynaptic areas. In this study, we set out to investigate the role that tyrosine kinase might play presynaptically to modulate release of glutamate in an effort to understand the mechanism underlying the persistent increase in release that accompanies LTP in perforant path-granule cell synapses. We report that LTP was associated with increased calcium influx and glutamate release. LTP was also associated with an increase in phosphorylation of the α-subunit of calcium channels and ERK in synaptosomes prepared from dentate gyrus, and these effects were inhibited when LTP was blocked by the tyrosine kinase inhibitor, genistein. LTP was accompanied by increased protein synthesis and increased phosphorylation of CREB in entorhinal cortex, effects that were also blocked by genistein. We conclude that tetanic stimulation leads to enhanced tyrosine phosphorylation of certain presynaptically located proteins that modulate glutamate release and contribute to expression of LTP.

Original languageEnglish
Pages (from-to)377-385
Number of pages9
JournalHippocampus
Volume12
Issue number3
DOIs
Publication statusPublished - 2002
Externally publishedYes

Keywords

  • Calcium channel α-subunit
  • Calcium influx
  • CREB
  • ERK
  • Glutamate release

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