title: NMDA receptor activation strengthens weak electrical coupling in mammalian brain.
abstract: Electrical synapses are formed by gap junctions and permit electrical coupling, which shapes the synchrony of neuronal ensembles. Here, we provide a direct demonstration of receptor-mediated strengthening of electrical coupling in mammalian brain. Electrical coupling in the inferior olive of rats was strengthened by activation of NMDA-type glutamate receptors (NMDARs), which were found at synaptic loci and at extrasynaptic loci 20-100 nm proximal to gap junctions. Electrical coupling was strengthened by pharmacological and synaptic activation of NMDARs, whereas costimulation of ionotropic non-NMDAR glutamate receptors transiently antagonized the effect of NMDAR activation. NMDAR-dependent strengthening (1) occurred despite increased input conductance, (2) induced Ca(2+)-influx microdomains near dendritic spines, (3) required activation of the Ca(2+)/calmodulin-dependent protein-kinase II, (4) was restricted to neurons that were weakly coupled, and (5) thus strengthened coupling, mainly between nonadjacent neurons. This provided a mechanism to expand the synchronization of rhythmic membrane potential oscillations by chemical neurotransmitter input.
authors.affiliation: Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Josef
authors.initials: J
authors.lastname: Turecek
authors.affiliation: Department of Psychiatry, New York Presbyterian Hospital-Weill Cornell Medical College, 525 East 68(th) Street, New York, NY 10065, USA.
authors.forename: Genevieve S
authors.initials: GS
authors.lastname: Yuen
authors.affiliation: Center for Integrative Brain Research, Seattle Children's Research Institute, 1900 9(th) Avenue, Seattle, WA 98155, USA.
authors.forename: Victor Z
authors.initials: VZ
authors.lastname: Han
authors.affiliation: Center for Integrative Brain Research, Seattle Children's Research Institute, 1900 9(th) Avenue, Seattle, WA 98155, USA.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Zeng
authors.affiliation: Department of Pharmacology, University of Colorado-Denver School of Medicine, 12800 E. 19(th) Avenue, Aurora, CO 80045, USA.
authors.forename: K Ulrich
authors.initials: KU
authors.lastname: Bayer
authors.affiliation: Center for Integrative Brain Research, Seattle Children's Research Institute, 1900 9(th) Avenue, Seattle, WA 98155, USA; Department of Pediatrics, University of Washington, 1959 N.E. Pacific Street, Seattle, WA 98195, USA. Electronic address: john.welsh@seattlechildrens.org.
authors.forename: John P
authors.initials: JP
authors.lastname: Welsh
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D049229:Dendritic Spines / Q000187:drug effects / Q000648:ultrastructure; D054351:Electrical Synapses / Q000187:drug effects / Q000378:metabolism*; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D002118:Calcium