NMDA receptor activation strengthens weak electrical coupling in mammalian brain

Neuron. 2014 Mar 19;81(6):1375-1388. doi: 10.1016/j.neuron.2014.01.024.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Calcium / metabolism*
  • Dendritic Spines / drug effects
  • Dendritic Spines / ultrastructure
  • Electrical Synapses / drug effects
  • Electrical Synapses / metabolism*
  • Gap Junctions / drug effects
  • Gap Junctions / metabolism*
  • Ion Transport / drug effects
  • Ion Transport / physiology
  • Membrane Potentials* / drug effects
  • Membrane Potentials* / physiology
  • N-Methylaspartate / pharmacology
  • Neurons / drug effects
  • Neurons / ultrastructure
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / metabolism


  • Receptors, N-Methyl-D-Aspartate
  • N-Methylaspartate
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Calcium