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

doi:10.1038/nn1449

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

Obstetrics and Gynecology

Research output: Contribution to journal › Article › peer-review

396 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 language	English (US)
Pages (from-to)	642-649
Number of pages	8
Journal	Nature Neuroscience
Volume	8
Issue number	5
DOIs	https://doi.org/10.1038/nn1449
State	Published - May 2005

Funding

We thank T. Tzounopoulos and C. Jahr for helpful discussions. We also thank G. Banker and S. Kaech-Petrie for assistance with hippocampal cultures. This work was supported by National Institutes of Health grants to J.M. and J.P.A., and by grants to B.L.S. from the Whitaker Foundation and the Searle Scholar’s program.

Funders
Author National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health The Bev Hartig Huntington's Disease Foundation National Institutes of Health
Whitaker Foundation

ASJC Scopus subject areas

General Neuroscience

Access to Document

10.1038/nn1449

Cite this

@article{5d5b29cb9f7841d5bc02675abfce9549,

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

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.",

author = "Ngo-Anh, \{Thu Jennifer\} and Bloodgood, \{Brenda L.\} and Michael Lin and Sabatini, \{Bernardo L.\} and James Maylie and Adelman, \{John P.\}",

note = "Funding Information: We thank T. Tzounopoulos and C. Jahr for helpful discussions. We also thank G. Banker and S. Kaech-Petrie for assistance with hippocampal cultures. This work was supported by National Institutes of Health grants to J.M. and J.P.A., and by grants to B.L.S. from the Whitaker Foundation and the Searle Scholar{\textquoteright}s program.",

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AU - Bloodgood, Brenda L.

AU - Lin, Michael

AU - Sabatini, Bernardo L.

AU - Maylie, James

AU - Adelman, John P.

N1 - Funding Information: We thank T. Tzounopoulos and C. Jahr for helpful discussions. We also thank G. Banker and S. Kaech-Petrie for assistance with hippocampal cultures. This work was supported by National Institutes of Health grants to J.M. and J.P.A., and by grants to B.L.S. from the Whitaker Foundation and the Searle Scholar’s program.

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N2 - 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.

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