Influx of extracellular calcium regulates actin-dependent morphological plasticity in dendritic spines

Ina Brünig, Stefanie Kaech, Heike Brinkhaus, Thomas G. Oertner, Andrew Matus

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Dendritic spines contain a specialized cytoskeleton composed of dynamic actin filaments capable of producing rapid changes in their motility and morphology. Transient changes in Ca2+ levels in the spine cytoplasm have been associated with the modulation of these effects in a variety of ways. To characterize the contribution of Ca2+ fluxes originating through different pathways to these phenomena, we used time-lapse imaging of cultured hippocampal neurons expressing GFP-actin to follow the influence of postsynaptic neurotransmitter receptors, voltage-activated Ca2+ channels and release from internal Ca2+ stores on spine actin dynamics. Stimulation of AMPA receptors produced a rapid blockade of actin-dependent spine motility that was immediately reversible when AMPA was removed. Stimulation of NMDA receptors also blocked spine motility but in this case suppression of actin dynamics was delayed by up to 30 min depending on NMDA concentration and motility was never seen to recover when NMDA was removed. These effects could be mimicked by depolarizing neurons under appropriate circumstances demonstrating the involvement of voltage-activated Ca2+ channels in AMPA receptor-mediated effects and the receptor associated Ca2+ channel in the effects of NMDA. Caffeine, an agent that releases Ca2+ from internal stores, had no immediate effect on spine actin, a result compatible with the lack of caffeine-releasable Ca2+ in cultured hippocampal neurons under resting conditions. Blocking internal store function by thapsigargin led to a delayed suppression of spine actin dynamics that was dependent on extracellular Ca2+. Together these results indicate the common involvement of changes in Ca2+ levels in modulating actin-dependent effects on dendritic spine motility and morphology through several modes of electrophysiological activation.

Original languageEnglish (US)
Pages (from-to)669-676
Number of pages8
JournalNeuropharmacology
Volume47
Issue number5
DOIs
StatePublished - Oct 1 2004

Keywords

  • Cytoskeleton
  • Dendritic spines
  • Excitatory synapse
  • Glutamate receptor
  • Hippocampus
  • Synaptic plasticity

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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