Regulation of dendritic calcium release in striatal spiny projection neurons

Joshua L. Plotkin, Weixing Shen, Igor Rafalovich, Luke E. Sebel, Michelle Day, C. Savio Chan, D. James Surmeier*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


The induction of corticostriatal long-term depression (LTD) in striatal spiny projection neurons (SPNs) requires coactivation of group I metabotropic glutamate receptors (mGluRs) and L-type Ca2++ channels. This combination leads to the postsynaptic production of endocannabinoids that act presynaptically to reduce glutamate release. Although the necessity of coactivation is agreed upon, why it is necessary in physiologically meaningful settings is not. The studies described here attempt to answer this question by using two-photon laser scanning microscopy and patch-clamp electrophysiology to interrogate the dendritic synapses of SPNs in ex vivo brain slices from transgenic mice. These experiments revealed that postsynaptic action potentials induce robust ryanodine receptor (RYR)-dependent Ca2++-induced- Ca2++ release (CICR) in SPN dendritic spines. Depolarization-induced opening of voltage-gated Ca2++ channels was necessary for CICR. CICR was more robust in indirect pathway SPNs than in direct pathway SPNs, particularly in distal dendrites. Although it did not increase intracellular Ca2+ concentration alone, group I mGluR activation enhanced CICR and slowed Ca2++ clearance, extending the activity-evoked intraspine transient. The mGluR modulation of CICR was sensitive to antagonism of inositol trisphosphate receptors, RYRs, src kinase, and Cav1.3 L-type Ca2++ channels. Uncaging glutamate at individual spines effectively activated mGluRs and facilitated CICR induced by back-propagating action potentials. Disrupting CICR by antagonizing RYRs prevented the induction of corticostriatal LTD with spike-timing protocols. In contrast, mGluRs had no effect on the induction of long-term potentiation. Taken together, these results make clearer how coactivation of mGluRs and L-type Ca2++ channels promotes the induction of activity-dependent LTD in SPNs.

Original languageEnglish (US)
Pages (from-to)2325-2336
Number of pages12
JournalJournal of neurophysiology
Issue number10
StatePublished - Nov 15 2013


  • Calcium
  • Long-term depression
  • Plasticity
  • Striatum
  • Two-photon imaging

ASJC Scopus subject areas

  • Physiology
  • General Neuroscience


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