Calmodulin controls synaptic strength via presynaptic activation of calmodulin kinase II

Zhiping P. Pang, Peng Cao, Wei Xu, Thomas C. Südhof

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

Calmodulin regulates multifarious cellular processes via a panoply of target interactions. However, the central role, multiple isoforms, and complex target interactions of calmodulin make it difficult to examine its precise functions. Here, we analyzed calmodulin function in neurons using lentivirally delivered short-hairpin RNAs that suppressed expression of all calmodulin isoforms by ∼70%. Calmodulin knockdown did not significantly alter neuronal survival or synapse formation but depressed spontaneous neuronal network activity. Strikingly, calmodulin knockdown decreased the presynaptic release probability almost twofold, without altering the presynaptic readily-releasable vesicle pool or postsynaptic neurotransmitter reception. In calmodulin knockdown neurons, presynaptic release was restored to wild-type levels by expression of constitutively active calmodulin-dependent kinase-IIα (CaMKIIα); in contrast, in control neurons, expression of constitutively active CaMKIIα had no effect on presynaptic release. Viewed together, these data suggest that calmodulin performs a major function in boosting synaptic strength via direct activation of presynaptic calmodulin-dependent kinase II.

Original languageEnglish (US)
Pages (from-to)4132-4142
Number of pages11
JournalJournal of Neuroscience
Volume30
Issue number11
DOIs
Publication statusPublished - Mar 17 2010

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ASJC Scopus subject areas

  • Neuroscience(all)

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