title: Regulation of dendritic calcium release in striatal spiny projection neurons.
abstract: 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 Ca(2+) 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 Ca(2+)-induced-Ca(2+) release (CICR) in SPN dendritic spines. Depolarization-induced opening of voltage-gated Ca(2+) 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 Ca(2+) concentration alone, group I mGluR activation enhanced CICR and slowed Ca(2+) 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 Ca(2+) 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 Ca(2+) channels promotes the induction of activity-dependent LTD in SPNs.
authors: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors: Joshua L
authors: JL
authors: Plotkin
authors: Weixing
authors: W
authors: Shen
authors: Igor
authors: I
authors: Rafalovich
authors: Luke E
authors: LE
authors: Sebel
authors: Michelle
authors: M
authors: Day
authors: C Savio
authors: CS
authors: Chan
authors: D James
authors: DJ
authors: Surmeier
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D003712:Dendrites / Q000378:metabolism*; D005260:Female; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000235:genetics; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors; D013569:Synapses / Q000502:physiology
chemical_list: D020746:Calcium Channels, L-Type; D011954:Receptors, Dopamine; D018094:Receptors, Metabotropic Glutamate; D008734:Methoxyhydroxyphenylglycol; D002118:Calcium; C010117:3,4-dihydroxyphenylglycol
keywords: calcium; long-term depression; plasticity; striatum; two-photon imaging
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