NMDA receptor activation limits the number of synaptic connections during hippocampal development

Nat Neurosci. 2001 Nov;4(11):1102-7. doi: 10.1038/nn744.

Abstract

Activity-dependent synaptic plasticity triggered by N-methyl-d-aspartate (NMDA) receptor activation is a fundamental property of many glutamatergic synapses and may be critical for the shaping and refinement of the structural and functional properties of neuronal circuits during early postnatal development. Using a combined morphological and electrophysiological approach, we showed that chronic blockade of NMDA receptors in hippocampal slice cultures during the first two weeks of postnatal development leads to a substantial increase in synapse number and results in a more complex dendritic arborization of CA1 pyramidal cells. Thus, the development of excitatory circuitry in the hippocampus is determined by two opposing processes: NMDA receptor-independent synapse formation and NMDA receptor-dependent attenuation of synaptogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Animals
  • Animals, Newborn
  • Cell Surface Extensions
  • Cells, Cultured
  • Dendrites / metabolism*
  • Dizocilpine Maleate / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / physiology
  • Hippocampus / cytology
  • Hippocampus / growth & development*
  • Histocytochemistry
  • In Vitro Techniques
  • Ion Channels / antagonists & inhibitors
  • Lysine / analogs & derivatives*
  • Microscopy, Confocal
  • Patch-Clamp Techniques
  • Piperazines / pharmacology
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology*
  • Pyramidal Cells / ultrastructure
  • Rats
  • Rats, Wistar
  • Receptors, AMPA / metabolism
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Synapses / metabolism
  • Synapses / physiology*

Substances

  • Excitatory Amino Acid Antagonists
  • Ion Channels
  • Piperazines
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Dizocilpine Maleate
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
  • biocytin
  • Lysine