Functional maturation of CA1 synapses involves activity-dependent loss of tonic kainate receptor-mediated inhibition of glutamate release

Neuron. 2006 May 4;50(3):415-29. doi: 10.1016/j.neuron.2006.03.020.


Early in development, excitatory synapses transmit with low efficacy, one mechanism for which is a low probability of transmitter release (Pr). However, little is known about the developmental mechanisms that control activity-dependent maturation of the presynaptic release. Here, we show that during early development, transmission at CA3-CA1 synapses is regulated by a high-affinity, G protein-dependent kainate receptor (KAR), which is endogenously activated by ambient glutamate. By tonically depressing glutamate release, this mechanism sets the dynamic properties of neonatal inputs to favor transmission during high frequency bursts of activity, typical for developing neuronal networks. In response to induction of LTP, the tonic activation of KAR is rapidly down regulated, causing an increase in Pr and profoundly changing the dynamic properties of transmission. Early development of the glutamatergic connectivity thus involves an activity-dependent loss of presynaptic KAR function producing maturation in the mode of excitatory transmission from CA3 to CA1.

Publication types

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

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Aging / physiology
  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Glutamic Acid / metabolism*
  • Hippocampus / cytology
  • Hippocampus / growth & development*
  • Hippocampus / metabolism
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Neural Pathways / cytology
  • Neural Pathways / growth & development*
  • Neural Pathways / metabolism
  • Organ Culture Techniques
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism*
  • Presynaptic Terminals / ultrastructure
  • Rats
  • Receptors, G-Protein-Coupled / drug effects
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Kainic Acid / drug effects
  • Receptors, Kainic Acid / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology


  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Receptors, G-Protein-Coupled
  • Receptors, Kainic Acid
  • Glutamic Acid