Enhancement of presynaptic neuronal excitability by correlated presynaptic and postsynaptic spiking

Nat Neurosci. 2000 Oct;3(10):1018-26. doi: 10.1038/79838.


Use-dependent modifications, such as long-term potentiation (LTP) of synaptic efficacy, are believed to be essential for information storage in the nervous system. Repetitive correlated spiking of presynaptic and postsynaptic neurons can induce LTP at excitatory glutamatergic synapses. In cultured hippocampal neurons, we show that repetitive correlated activity also results in a rapid and persistent enhancement of presynaptic excitability, decreasing the threshold for spiking and reducing the variability of interspike intervals. Furthermore, we found that correlated activity modified sodium channel gating in the presynaptic neuron. This modification of presynaptic excitability required a temporal order between presynaptic and postsynaptic spiking and activation of postsynaptic NMDA receptors. Presynaptic inhibition of protein kinase C abolished the change in excitability without affecting LTP. Such rapid activity-dependent changes in the efficacy of presynaptic spiking may be involved in the processing and storage of information within the nervous system.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology
  • Cells, Cultured
  • Fetus
  • Glutamic Acid / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Hippocampus / ultrastructure
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Patch-Clamp Techniques
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism*
  • Presynaptic Terminals / ultrastructure
  • Protein Kinase C / drug effects
  • Protein Kinase C / metabolism
  • Rats
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synaptic Membranes / drug effects
  • Synaptic Membranes / metabolism*
  • Synaptic Membranes / ultrastructure
  • Time Factors
  • gamma-Aminobutyric Acid / metabolism


  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Protein Kinase C