Calcium release from presynaptic ryanodine-sensitive stores is required for long-term depression at hippocampal CA3-CA3 pyramidal neuron synapses

Vivek K. Unni, Stanislav S. Zakharenko, Leonard Zablow, Anthony J. DeCostanzo, Steven A. Siegelbaum

Research output: Contribution to journalArticle

51 Scopus citations


Although Ca2+ release from internal stores has been proposed to be important for the induction of long-term synaptic plasticity, the importance of Ca2+ stores localized in presynaptic terminals remains unclear. Here, we have selectively applied pharmacological antagonists to either the presynaptic or postsynaptic cell in paired whole-cell recordings from hippocampal CA3 pyramidal neurons in slice culture. We demonstrate directly the necessary role of presynaptic, but not postsynaptic, ryanodine-sensitive Ca 2+ stores in the induction of NMDA receptor (NMDAR)-dependent long-term depression (LTD). Using two-photon laser scanning microscopy, we further find that release from the ryanodine-sensitive stores during prolonged synaptic stimulation generates a slowly rising Ca2+ signal in the presynaptic terminal that is required for the induction of LTD. Moreover, this form of LTD has a significant presynaptic component of expression because it causes a marked decrease in the rate of release from CA3 neuron presynaptic terminals of FM 1-43, a fluorescent probe of synaptic vesicle cycling. Thus, Ca2+ release from presynaptic ryanodine-sensitive stores is critical in the induction of a presynaptic component of NMDAR-dependent LTD.

Original languageEnglish (US)
Pages (from-to)9612-9622
Number of pages11
JournalJournal of Neuroscience
Issue number43
StatePublished - Oct 27 2004



  • CA3
  • Hippocampus
  • Internal calcium stores
  • Long-term depression
  • Ryanodine-sensitive stores
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

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