Tissue plasminogen activator contributes to the late phase of LTP and to synaptic growth in the hippocampal mossy fiber pathway

Neuron. 1998 Oct;21(4):813-25. doi: 10.1016/s0896-6273(00)80597-8.


The expression of tissue plasminogen activator (tPA) is increased during activity-dependent forms of synaptic plasticity. We have found that inhibitors of tPA inhibit the late phase of long-term potentiation (L-LTP) induced by either forskolin or tetanic stimulation in the hippocampal mossy fiber and Schaffer collateral pathways. Moreover, application of tPA enhances L-LTP induced by a single tetanus. Exposure of granule cells in culture to forskolin results in secretion of tPA, elongation of mossy fiber axons, and formation of new, active presynaptic varicosities contiguous to dendritic clusters of the glutamate receptor R1. These structural changes are blocked by tPA inhibitors and induced by application of tPA. Thus, tPA may be critically involved in the production of L-LTP and specifically in synaptic growth.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Axons / drug effects
  • Cells, Cultured
  • Colforsin / pharmacology
  • Cycloheptanes
  • Electric Stimulation
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • In Vitro Techniques
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Mossy Fibers, Hippocampal / drug effects
  • Mossy Fibers, Hippocampal / physiology*
  • Neural Pathways / drug effects
  • Neural Pathways / physiology
  • Neurons / metabolism
  • Plasminogen Activator Inhibitor 1 / pharmacology
  • Presynaptic Terminals / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Serine Proteinase Inhibitors / pharmacology
  • Synapses / physiology*
  • Tissue Plasminogen Activator / antagonists & inhibitors
  • Tissue Plasminogen Activator / metabolism
  • Tissue Plasminogen Activator / pharmacology
  • Tissue Plasminogen Activator / physiology*


  • Cycloheptanes
  • Plasminogen Activator Inhibitor 1
  • Serine Proteinase Inhibitors
  • tPA stop
  • Colforsin
  • Tissue Plasminogen Activator