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Tissue-plasminogen activator is induced as an immediate–early gene during seizure, kindling and long-term potentiation

Nature volume 361, pages 453–457 (1993)Cite this article

Abstract

THE requirement of protein and messenger RNA synthesis for long-term memory1,2 suggests that neural activity induced by learning initiates a cascade of gene expression3. Here we use differential screening to identify five immediate–early genes induced by neuronal activity. One of these is tissue-plasminogen activator (tPA), an extracellular serine protease, which is induced with different spatial patterns in the brain by three activity-dependent events: (1) convulsive seizure increases expression of tPA in the whole brain; (2) stimulation of the perforant path produces an epileptiform after-discharge that ultimately leads to kindling increases the levels of tPA throughout the hippocampus bilaterally; and (3) brief high-frequency stimulation of the perforant path that produces long-term potentiation (LTP) causes an NMDA (N -methyl-D-aspartate) receptor-mediated increase in the levels of tPA mRNA which is restricted to the granule cells of the ipsilateral dentate gyrus. As release of tPA is correlated with morphological differentiation4–6, the increased expression of tPA may play a role in the structural changes that accompany activity-dependent plasticity7–10.

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  1. Mary E. Gilbert: ManTech Environmental Technology Inc., PO Box 12313, Research Triangle Park, North Carolina 27709, USA

Authors and Affiliations

  1. Center for Neurobiology and Behavior, and Howard Hughes Medical Institute, College of Physicians and Surgeons of Columbia University, 722 West 168th Street, New York, New York, 10032, USA

    Zhuo Qian, Mary E. Gilbert, Michael A. Colicos, Eric R. Kandel & Dietmar Kuhl

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  1. Zhuo Qian
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Qian, Z., Gilbert, M., Colicos, M. et al. Tissue-plasminogen activator is induced as an immediate–early gene during seizure, kindling and long-term potentiation. Nature 361, 453–457 (1993). https://doi.org/10.1038/361453a0

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