Nature Neuroscience8, 642 - 649 (2005)
Published online: 24 April 2005; | doi:10.1038/nn1449
SK channels and NMDA receptors form a Ca2+-mediated feedback loop in dendritic spines
Thu Jennifer Ngo-Anh1, 4, Brenda L Bloodgood2, 4, Michael Lin1, Bernardo L Sabatini2, James Maylie3
& John P Adelman1
1
Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
2
Department of Neurobiology, Harvard Medical School, 200 Longwood Ave., Goldenson 316, Boston, Massachusetts 02115, USA.
3
Department of Obstetrics and Gynecology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
4
These authors contributed equally to this work.
Correspondence should be addressed to John P Adelman adelman@ohsu.edu
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.
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
