Presynaptic modulation of cortical synaptic activity by calcineurin

Ronald G. Victor, Gail Thomas, Eduardo Marban, Brian O'Rourke

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

Synaptic plasticity is modulated by Ca2+-induced alterations in the balance between phosphorylation and dephosphorylation. Recent evidence suggests that calcineurin, the Ca2+-calmodulin-dependent phosphatase (2B), modulates the activity of postsynaptic glutamate receptors. However, in rat cortex, calcineurin is enriched mainly in presynaptic, not postsynaptic, fractions. To determine if calcineurin modulates glutamatergic neurotransmission through a presynaptic mechanism, we used whole-cell patch clamp experiments to test effects of two specific calcineurin inhibitors, cyclosporin A (CsA) and FK506, on synaptic activity in fetal rat cortical neurons. The rate of spontaneous action-potential firing was markedly increased by either CsA or FK506 but was unaffected by rapamycin, a structural analog of FK506 which has no effect on calcineurin. In voltage- clamp experiments, CsA increased the rate but not the amplitude of glutamate receptor-mediated, excitatory postsynaptic currents, suggesting an increased rate of glutamate release. CsA had no effect on the amplitude of currents evoked by brief bath application of selective glutamate receptor agonists, providing further evidence for a pre- rather than postsynaptic site of action. In conclusion, these data indicate that calcineurin modulates glutamatergic neurotransmission in rat cortical neurons through a presynaptic mechanism.

Original languageEnglish (US)
Pages (from-to)6269-6273
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number14
DOIs
StatePublished - Jul 3 1995

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Calcineurin
Cyclosporine
Glutamate Receptors
Tacrolimus
Synaptic Transmission
Excitatory Amino Acid Agonists
Neurons
Fetal Movement
Neuronal Plasticity
Excitatory Postsynaptic Potentials
Sirolimus
Calmodulin
Baths
Phosphoric Monoester Hydrolases
Action Potentials
Glutamic Acid
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Genetics
  • General

Cite this

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Presynaptic modulation of cortical synaptic activity by calcineurin. / Victor, Ronald G.; Thomas, Gail; Marban, Eduardo; O'Rourke, Brian.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 14, 03.07.1995, p. 6269-6273.

Research output: Contribution to journalArticle

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