A different form of long-lasting potentiation revealed in tissue plasminogen activator mutant mice

Julietta Uta Frey, Michael Müller, Dietmar Kuhl

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181 Scopus citations


The establishment of hippocampal long-term potentiation (LTP) requires protein and mRNA synthesis, suggesting that neuronal activity resulting in LTP initiates a cascade of gene expression. The expression of the gene for the extracellular serine protease tissue plasminogen activator (t-PA) is induced during LTP. Here we analyze long-lasting LTP (L-LTP, >4 hr) in CA1 hippocampal slices of mice homozygous for disrupted t-PA genes. Although mutant mice appear to exhibit long-term potentiation, we provide evidence that these mice are devoid of conventional, homosynaptic L-LTP at the Schaffer collateral-CA1 pyramidal cell synapse. Most remarkably, t-PA- deficient mice exhibit a different form of long-lasting potentiation that is characterized by an NMDA receptor-dependent modification of GABA transmission in the CA1 region.

Original languageEnglish (US)
Pages (from-to)2057-2063
Number of pages7
JournalJournal of Neuroscience
Issue number6
Publication statusPublished - Mar 15 1996



  • GABAergic transmission
  • gene induction
  • hippocampus
  • long-term potentiation
  • neuronal plasticity
  • tissue plasminogen activator

ASJC Scopus subject areas

  • Neuroscience(all)

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