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Enhanced hippocampal long‐term potentiation and learning by increased neuronal expression of tissue‐type plasminogen activator in transgenic mice
Author(s) -
Madani Rime,
Hulo Sophie,
Toni Nicolas,
Madani Hala,
Steimer Thierry,
Muller Dominique,
Vassalli JeanDominique
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.11.3007
Subject(s) - biology , long term potentiation , hippocampal formation , plasminogen activator , transgene , activator (genetics) , genetically modified mouse , microbiology and biotechnology , t plasminogen activator , tissue plasminogen activator , neuroscience , term (time) , endocrinology , biochemistry , receptor , gene , physics , quantum mechanics
Adult cortical neurons can produce tissue‐type plasminogen activator (tPA), an extracellular protease that plays a critical role in fibrinolysis and tissue remodelling processes. There is growing evidence that extracellular proteolysis may be involved in synaptic plasticity, axonal remodelling and neurotoxicity in the adult central nervous system. Here we show that transgenic mice overexpressing tPA in post‐natal neurons have increased and prolonged hippocampal long‐term potentiation (LTP), and improved performance in spatial orientation learning tasks. Extracellular proteolysis catalysed by tPA may facilitate synaptic micro‐remodelling, and thereby play a role in activity‐dependent neuronal plasticity and learning.