Enhanced hippocampal long-term potentiation and learning by increased neuronal expression of tissue-type plasminogen activator in transgenic mice

Adult cortical neurons can produce tissue-type plasminogen activator (tPA), an extracellular protease that plays a critical role in fibrinolysis and t issue remodelling processes. There is growing evidence that extracellular p roteolysis may be involved in synaptic plasticity, axonal remodelling and n eurotoxicity in the adult central nervous system. Here we show that transge nic mice overexpressing tPA in post-natal neurons have increased and prolon ged hippocampal long-term potentiation (LTP), and improved performance in s patial orientation learning tasks. Extracellular proteolysis catalysed by t PA may facilitate synaptic micro-remodelling, and thereby play a role in ac tivity-dependent neuronal plasticity and learning.