Tissue plasminogen activator is required for corticostriatal long-term potentiation

Diego Centonze, Maddalena Napolitano, Emilia Saulle, Paolo Gubellini, Barbara Picconi, Alessandro Martorana, Antonio Pisani, Alberto Gulino, Giorgio Bernardi, Paolo Calabresi

Research output: Contribution to journalArticlepeer-review


Several experimental data indicate that tissue plasminogen activator (tPA) is involved in memory formation and synaptic plasticity in different brain areas. In the attempt to highlight the role of this serine protease in striatal neuron activity, mice lacking tPA have been used for electrophysiological, immunohistochemical and Western blot experiments. Disruption of tPA gene prevented corticostriatal long-term potentiation, an NMDA-dependent form of synaptic plasticity requiring the stimulation of both dopamine and acetylcholine receptors. Spontaneous and evoked glutamatergic transmission was intact in the striatum of tPA-deficient mice, as was the nigrostriatal dopamine innervation and the expression of dopamine D1 receptors. Conversely, the sensitivity of striatal cholinergic interneurons to dopamine D1 receptor stimulation was lost in these mutants, suggesting that tPA facilitates long-term potentiation (LTP) induction in the striatum by favouring the D1 receptor-mediated excitation of acetylcholine-producing interneurons. The demonstration that tPA ablation interferes with the induction of corticostriatal LTP and with the dopamine receptor-mediated control of cholinergic interneurons might help to explain the altered striatum-dependent learning deficits observed in tPA-deficient mice and provides new insights into the molecular mechanisms underlying synaptic plasticity in the striatum.

Original languageEnglish
Pages (from-to)713-721
Number of pages9
JournalEuropean Journal of Neuroscience
Issue number4
Publication statusPublished - 2002


  • Dopamine receptors
  • Motor learning
  • Tyrosine hydroxylase
  • Western blot

ASJC Scopus subject areas

  • Neuroscience(all)


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