title: Retrograde synaptic signaling mediated by K+ efflux through postsynaptic NMDA receptors.
abstract: Synaptic NMDA receptors (NMDARs) carry inward Ca(2+) current responsible for postsynaptic signaling and plasticity in dendritic spines. Whether the concurrent K(+) efflux through the same receptors into the synaptic cleft has a physiological role is not known. Here, we report that NMDAR-dependent K(+) efflux can provide a retrograde signal in the synapse. In hippocampal CA3-CA1 synapses, the bulk of astrocytic K(+) current triggered by synaptic activity reflected K(+) efflux through local postsynaptic NMDARs. The local extracellular K(+) rise produced by activation of postsynaptic NMDARs boosted action potential-evoked presynaptic Ca(2+) transients and neurotransmitter release from Schaffer collaterals. Our findings indicate that postsynaptic NMDAR-mediated K(+) efflux contributes to use-dependent synaptic facilitation, thus revealing a fundamental form of retrograde synaptic signaling.
authors.affiliation: RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Shih
authors.affiliation: UCL Institute of Neurology, University College London, London WC1N 3BG, UK.
authors.forename: Leonid P
authors.initials: LP
authors.lastname: Savtchenko
authors.affiliation: National Institute for Physiological Sciences, Myodaiji, Okazaki 444-8787, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Kamasawa
authors.affiliation: RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan; University of Nizhny Novgorod, Nizhny Novgorod 603950, Russia.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Dembitskaya
authors.affiliation: RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: McHugh
authors.affiliation: UCL Institute of Neurology, University College London, London WC1N 3BG, UK.
authors.forename: Dmitri A
authors.initials: DA
authors.lastname: Rusakov
authors.affiliation: National Institute for Physiological Sciences, Myodaiji, Okazaki 444-8787, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Shigemoto
authors.affiliation: RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan; University of Nizhny Novgorod, Nizhny Novgorod 603950, Russia. Electronic address: semyanov@brain.riken.jp.
authors.forename: Alexey
authors.initials: A
authors.lastname: Semyanov
mesh_terms: D000200:Action Potentials; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002118:Calcium / Q000737:chemistry; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D017136:Ion Transport / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D018698:Glutamic Acid; D011188:Potassium; D002118:Calcium