Activity-dependent plasticity of the NMDA-receptor fractional Ca2+ current

Neuron. 2007 Jan 4;53(1):17-24. doi: 10.1016/j.neuron.2006.11.016.

Abstract

Ca(2+) influx through NMDA receptors (NMDA-Rs) triggers synaptic plasticity, gene transcription, and cytotoxicity, but little is known about the regulation of NMDA-Rs themselves. We used two-photon glutamate uncaging to activate NMDA-Rs on individual dendritic spines in rat CA1 neurons while we measured NMDA-R currents at the soma and [Ca(2+)] changes in spines. Low-frequency uncaging trains induced Ca(2+)-dependent long-term depression of NMDA-R-mediated synaptic currents. Additionally, uncaging trains caused a reduction in the Ca(2+) accumulation per unit of NMDA-R current in spines due to a reduction in the fraction of the NMDA-R current carried by Ca(2+). Induction of depression of NMDA-R-mediated Ca(2+) influx required activation of NR2B-containing receptors. Receptors in single spines depressed rapidly in an all-or-none manner. These adaptive changes in NMDA-R function likely play a critical role in metaplasticity and in stabilizing activity levels in neuronal networks with Hebbian synapses.

Publication types

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

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology*
  • Dendritic Spines / drug effects
  • Dendritic Spines / metabolism*
  • Dendritic Spines / ultrastructure
  • Glutamic Acid / metabolism
  • Glutamic Acid / pharmacology
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Hippocampus / ultrastructure
  • Long-Term Synaptic Depression / drug effects
  • Long-Term Synaptic Depression / physiology
  • Nerve Net / drug effects
  • Nerve Net / metabolism
  • Nerve Net / ultrastructure
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism
  • Neural Pathways / ultrastructure
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Organ Culture Techniques
  • Patch-Clamp Techniques
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism
  • Pyramidal Cells / ultrastructure
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*

Substances

  • NR2B NMDA receptor
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • Calcium