Metaplasticity at Single Glutamatergic Synapses

Neuron. 2010 Jun 24;66(6):859-70. doi: 10.1016/j.neuron.2010.05.015.

Abstract

Optimal function of neuronal networks requires interplay between rapid forms of Hebbian plasticity and homeostatic mechanisms that adjust the threshold for plasticity, termed metaplasticity. Numerous forms of rapid synapse plasticity have been examined in detail. However, the rules that govern synaptic metaplasticity are much less clear. Here, we demonstrate a local subunit-specific switch in NMDA receptors that alternately primes or prevents potentiation at single synapses. Prolonged suppression of neurotransmitter release enhances NMDA receptor currents, increases the number of functional NMDA receptors containing NR2B, and augments calcium transients at single dendritic spines. This local switch in NMDA receptors requires spontaneous glutamate release but is independent of action potentials. Moreover, single inactivated synapses exhibit a lower induction threshold for both long-term synaptic potentiation and plasticity-induced spine growth. Thus, spontaneous glutamate release adjusts plasticity threshold at single synapses by local regulation of NMDA receptors, providing a novel spatially delimited form of synaptic metaplasticity.

Publication types

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

MeSH terms

  • Anesthetics, Local / pharmacology
  • Animals
  • Biophysics / methods
  • Dendritic Spines / drug effects
  • Dendritic Spines / physiology
  • Electric Stimulation / methods
  • Embryo, Mammalian
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / genetics
  • Glutamic Acid / metabolism*
  • Green Fluorescent Proteins / genetics
  • Hippocampus / cytology
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / genetics
  • Models, Biological
  • Neuronal Plasticity / physiology*
  • Neurons / physiology*
  • Patch-Clamp Techniques / methods
  • Quinoxalines / pharmacology
  • Rats
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synapses / physiology*
  • Tetanus Toxin / genetics
  • Tetanus Toxin / metabolism
  • Tetrodotoxin / pharmacology
  • Time Factors
  • Transfection / methods
  • Valine / analogs & derivatives
  • Valine / pharmacology

Substances

  • Anesthetics, Local
  • Excitatory Amino Acid Antagonists
  • NR2B NMDA receptor
  • Quinoxalines
  • Receptors, N-Methyl-D-Aspartate
  • Tetanus Toxin
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • Green Fluorescent Proteins
  • Glutamic Acid
  • Tetrodotoxin
  • 2-amino-5-phosphopentanoic acid
  • Valine