A Developmental Switch in Neurotransmitter Flux Enhances Synaptic Efficacy by Affecting AMPA Receptor Activation

Neuron. 2001 Feb;29(2):469-84. doi: 10.1016/s0896-6273(01)00219-7.

Abstract

Formation of glutamatergic synapses entails development of "silent" immature contacts into mature functional synapses. To determine how this transformation occurs, we investigated the development of neurotransmission at single synapses in vitro. Maturation of presynaptic function, assayed with endocytotic markers, followed accumulation of synapsin I. During this period, synaptic transmission was primarily mediated by activation of NMDA receptors, suggesting that most synapses were functionally silent. However, local glutamate application to silent synapses indicated that these synapses contained functional AMPA receptors, suggesting a possible presynaptic locus for silent transmission. Interference with presynaptic vesicle fusion by exposure to tetanus toxin reverted functional to silent transmission, implicating SNARE-mediated fusion as a determinant of the ratio of NMDA:AMPA receptor activation. This work reveals that functional maturation of synaptic transmission involves transformation of presynaptic silent secretion into mature synaptic transmitter release.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Calcium / pharmacology
  • Cells, Cultured
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists / pharmacology
  • Hippocampus
  • Neuronal Plasticity / physiology
  • Quinoxalines / pharmacology
  • Rats
  • Receptors, AMPA / drug effects
  • Receptors, AMPA / physiology*
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Synapses / drug effects
  • Synapses / physiology*
  • Synapsins / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Synaptic Vesicles / drug effects
  • Synaptic Vesicles / physiology
  • Tetanus Toxin / pharmacology

Substances

  • Excitatory Amino Acid Antagonists
  • Quinoxalines
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Synapsins
  • Tetanus Toxin
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • Calcium