A proportional but slower NMDA potentiation follows AMPA potentiation in LTP

Nat Neurosci. 2004 May;7(5):518-24. doi: 10.1038/nn1220. Epub 2004 Mar 28.


Most excitatory glutamatergic synapses contain both AMPA and NMDA receptors, but whether these receptors are regulated together or independently during synaptic plasticity has been controversial. Although long-term potentiation (LTP) is thought to selectively enhance AMPA currents and alter the NMDA-to-AMPA ratio, this ratio is well conserved across synapses onto the same neuron. This suggests that the NMDA-to-AMPA ratio is only transiently perturbed by LTP. To test this, we induced LTP at rat neocortical synapses and recorded mixed AMPA-NMDA currents. We observed rapid LTP of AMPA currents, as well as delayed potentiation of NMDA currents that required previous AMPA potentiation. The delayed potentiation of NMDA currents restored the original NMDA-to-AMPA ratio within 2 h of LTP induction. These data suggest that recruitment of AMPA receptors to synapses eventually induces a proportional increase in NMDA current. This may ensure that LTP does not alter the relative contributions of these two receptors to synaptic transmission and information processing.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Drug Synergism
  • Electric Stimulation / methods
  • Excitatory Amino Acid Agonists / pharmacology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / radiation effects
  • In Vitro Techniques
  • Long-Term Potentiation / drug effects*
  • Long-Term Potentiation / radiation effects
  • N-Methylaspartate / pharmacology*
  • Neurons / drug effects*
  • Neurons / physiology
  • Neurons / radiation effects
  • Patch-Clamp Techniques / methods
  • Quinoxalines / pharmacology
  • Rats
  • Receptors, AMPA / metabolism
  • Sodium Channel Blockers / pharmacology
  • Synapses / drug effects
  • Synapses / radiation effects
  • Tetrodotoxin / pharmacology
  • Time Factors
  • Transfection / methods
  • Valine / analogs & derivatives*
  • Valine / pharmacology
  • Visual Cortex / cytology*
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology*


  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Quinoxalines
  • Receptors, AMPA
  • Sodium Channel Blockers
  • Tetrodotoxin
  • FG 9041
  • N-Methylaspartate
  • 2-amino-5-phosphopentanoic acid
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Valine
  • glutamate receptor ionotropic, AMPA 1