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Tissue plasminogen activator mediates reverse occlusion plasticity in visual cortex

Nature Neuroscience volume 1, pages 47–53 (1998)Cite this article

Abstract

Preventing visual input to one eye (monocular deprivation) in early postnatal development reduces cortical responses to stimulation of the deprived eye, with a significant loss of thalamocortical connections. These effects are reversible by opening the deprived eye and closing the previously open eye (reverse occlusion). We show that intracortical blockade of tissue plasminogen activator or plasmin selectively prevents recovery of cortical function and thalamic neuron size during reverse occlusion, without affecting the monocular deprivation response. Therefore, a proteolytic cascade consisting of plasmin generated by tissue plasminogen activator may selectively mediate reverse-occlusion-induced cortical plasticity, perhaps via structural remodeling of axons.

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Figure 1: Ocular dominance distributions in control and leupeptin-infused hemispheres.
Figure 2: Identification of proteases involved in RO plasticity.
Figure 3: tPA is expressed in kitten visual cortex and LGN.
Figure 4: Mean ratios of cell sizes in LGN layers receiving deprived input (closed) to those in layers with normal input (reopened) during RO.
Figure 5: Proteolytic activities in media conditioned by organotypic slice cultures sampled over 6 consecutive days following the 17th day in vitro.

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Acknowledgements

This study was supported by Boehringer Ingelheim Fonds to C.B.G and by DFG Mü908/3-1, European Commission (DG-XII/BIOTECH) and G.A.B.I. (III) to C.M.M. We appreciate the expert technical assistance by Veronica Dossinger, Uwe Fauser and Regina Ort and are indebted to Matthias Munk and Tobias Bonhoeffer for critical comments on an earlier version of the manuscript.

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  1. Both authors contributed to the experimental work of the study

Authors and Affiliations

  1. Max-Planck-Institute for Developmental Biology, Spemannstr. 35/1, Tübingen, 72076, Germany

    Christian M. Müller

  2. Department of Physiology, University College London, Gower Street, London, WC1E 6 BT, UK

    Claudius B. Griesinger

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Correspondence to Christian M. Müller.

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Müller, C., Griesinger, C. Tissue plasminogen activator mediates reverse occlusion plasticity in visual cortex. Nat Neurosci 1, 47–53 (1998). https://doi.org/10.1038/248

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