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

Samuel S.H. Wang, Leonard Khiroug, George J. Augustine

Research output: Contribution to journalArticle

84 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)8635-8640
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number15
DOIs
StatePublished - Jul 18 2000

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Calcium
  • Flash photolysis
  • Glutamate receptors
  • Synaptic plasticity

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