title: Tissue plasminogen activator is required for corticostriatal long-term potentiation.
abstract: 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.
authors.affiliation: Clinica Neurologica, Dipartimento di Neuroscienze, Università di Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Centonze
authors.forename: Maddalena
authors.initials: M
authors.lastname: Napolitano
authors.forename: Emilia
authors.initials: E
authors.lastname: Saulle
authors.forename: Paolo
authors.initials: P
authors.lastname: Gubellini
authors.forename: Barbara
authors.initials: B
authors.lastname: Picconi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Martorana
authors.forename: Antonio
authors.initials: A
authors.lastname: Pisani
authors.forename: Alberto
authors.initials: A
authors.lastname: Gulino
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bernardi
authors.forename: Paolo
authors.initials: P
authors.lastname: Calabresi
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology*; D003342:Corpus Striatum / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D010959:Tissue Plasminogen Activator / Q000172:deficiency*
chemical_list: D010959:Tissue Plasminogen Activator