SK channels and NMDA receptors form a Ca2+-mediated feedback loop in dendritic spines

Thu Jennifer Ngo-Anh, Brenda L. Bloodgood, Michael Lin, Bernardo L. Sabatini, James Maylie, John P. Adelman

Research output: Contribution to journalArticle

314 Scopus citations

Abstract

Small-conductance Ca2+-activated K+ channels (SK channels) influence the induction of synaptic plasticity at hippocampal CA3-CA1 synapses. We find that in mice, SK channels are localized to dendritic spines, and their activity reduces the amplitude of evoked synaptic potentials in an NMDA receptor (NMDAR)-dependent manner. Using combined two-photon laser scanning microscopy and two-photon laser uncaging of glutamate, we show that SK channels regulate NMDAR-dependent Ca2+ influx within individual spines. SK channels are tightly coupled to synaptically activated Ca2+ sources, and their activity reduces the amplitude of NMDAR-dependent Ca2+ transients. These effects are mediated by a feedback loop within the spine head; during an excitatory postsynaptic potential (EPSP), Ca2+ influx opens SK channels that provide a local shunting current to reduce the EPSP and promote rapid Mg2+ block of the NMDAR. Thus, blocking SK channels facilitates the induction of long-term potentiation by enhancing NMDAR-dependent Ca2+ signals within dendritic spines.

Original languageEnglish (US)
Pages (from-to)642-649
Number of pages8
JournalNature Neuroscience
Volume8
Issue number5
DOIs
StatePublished - May 2005

ASJC Scopus subject areas

  • Neuroscience(all)

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    Ngo-Anh, T. J., Bloodgood, B. L., Lin, M., Sabatini, B. L., Maylie, J., & Adelman, J. P. (2005). SK channels and NMDA receptors form a Ca2+-mediated feedback loop in dendritic spines. Nature Neuroscience, 8(5), 642-649. https://doi.org/10.1038/nn1449