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Quantification of spread of cerebellar long-term depression with chemical two-photon uncaging of glutamate

  1. George J. Augustine†
  1. Department of Neurobiology, Duke University Medical Center, Box 3209, Durham, NC 27710

  1. Edited by Charles F. Stevens, The Salk Institute for Biological Studies, La Jolla, CA, and approved May 3, 2000 (received for review September 27, 1999)

Abstract

Localized, chemical two-photon photolysis of caged glutamate was used to map the changes in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors caused by long-term synaptic depression (LTD) in cerebellar Purkinje cells. LTD produced by pairing parallel fiber activity with depolarization was accompanied by a decline in the response of Purkinje cells to uncaged glutamate that accounted for both the time course and magnitude of LTD. This depression of glutamate responses was observed not only at the site of parallel fiber stimulation but also at more distant sites. The amount of LTD decreased with distance and was half-maximal 50 μm away from the site of parallel fiber activity. Estimation of the number of parallel fibers active during LTD induction indicates that LTD modified glutamate receptors not only at active synapses but also at 600 times as many inactive synapses on a single Purkinje cell. Therefore, both active and inactive parallel fiber synapses can undergo changes at a postsynaptic locus as a result of associative pre- and postsynaptic activity.

Footnotes

    • ↵* Present address: Department of Molecular Biology, Princeton University, Princeton, NJ 08544.

    • ↵† To whom reprint requests should be addressed. E-mail: georgea{at}neuro.duke.edu.

    • This paper was submitted directly (Track II) to the PNAS office.

    • Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.130414597.

    • Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.130414597

  • Abbreviations

    AMPA,
    α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid;
    BAPTA,
    1,2-bis(2-aminophenoxy)-ethane-N,N,N′,N′-tetraacetic acid;
    CNB,
    carboxynitrobenzyl;
    CNQX,
    6-cyano-7-nitroquinoxaline-2,3-dione;
    LTD,
    long-term depression;
    PF,
    parallel fiber;
    SVD,
    singular value decomposition;
    EPSP,
    excitatory postsynaptic potential
    • Received September 27, 1999.

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