Cited by 104Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsTreatment of Major Depression

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

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Wang, Samuel S.-H., Khiroug, Leonard, Augustine, George J.·2000·Proceedings of the National Academy of Sciences

Abstract

Localized, chemical two-photon photolysis of caged glutamate was used to map the changes in alpha-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 microm 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.

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Cited by

Sorted by citations

Authors
Wang, S. S.-H., Khiroug, L., & Augustine, G. J.
Affiliations
  • Duke Medical Center (US)
  • Salk Institute for Biological Studies (US)
Corresponding author
Augustine, George J.
Venue
Proceedings of the National Academy of Sciences
Published
2000-07-11
Volume
97
Issue
15
Pages
8635-8640
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W1986155820
Cited by
104
References
1
Citations by year
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FWCI
4.01
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R01NS034045, NS-09457, F32NS009457, NS34045)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
long-term depression, Purkinje cells, caged glutamate, two-photon photolysis, AMPA receptors, parallel fiber synapses, synaptic plasticity, postsynaptic plasticity, associative plasticity, glutamate uncaging
MeSH terms
Animals, Cells, Cultured, Cerebellum, Glutamates, Purkinje Cells, Time Factors, Photons, Receptors, AMPA, Rats

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