Action of tachykinins in the rat hippocampus: modulation of inhibitory synaptic transmission

Eur J Neurosci. 2003 Jun;17(12):2639-47. doi: 10.1046/j.1460-9568.2003.02708.x.


Substance P and other neuropeptides of the tachykinin family can powerfully excite CA1 hippocampal interneurons present in the CA1 region. In the present work we show that, by exciting hippocampal interneurons, tachykinins can indirectly inhibit pyramidal neurons. We found that tachykinins caused a decrease in the inhibitory synaptic current interval and an increase in the inhibitory synaptic current amplitude in almost all pyramidal neurons tested. This effect was tetrodotoxin sensitive. Tachykinins did not alter the frequency or amplitude of miniature inhibitory synaptic currents and were without effect on evoked inhibitory synaptic currents. Thus, these neuropeptides acted at the somatodendritic membrane of GABAergic interneurons, rather than at their axon terminals. The effect of substance P on spontaneous inhibitory synaptic currents could be mimicked by a selective agonist of NK1 receptors, but not by selective agonists of NK2 and NK3 receptors. It was suppressed by an NK1 receptor antagonist. In CA1 interneurons located in stratum radiatum, substance P generated a sustained tetrodotoxin-insensitive inward current or induced membrane depolarization and action potential firing. This direct excitatory action was mediated by NK1 receptors. Current-voltage relationships indicate that the net tachykinin-evoked current reversed in polarity at or near the K+ equilibrium potential, suggesting that a suppression of a resting K+ conductance was involved. By increasing the excitability of CA1 GABAergic interneurons, tachykinins can powerfully facilitate the inhibitory synaptic input to pyramidal neurons. This indirect inhibition could play a role in regulating short-term and/or long-term synaptic plasticity, promoting neuronal circuit synchronization or, in some physiopathological situations, influencing epileptogenesis.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Bicuculline / pharmacology
  • Drug Interactions
  • Excitatory Amino Acid Antagonists / pharmacology
  • GABA Antagonists / pharmacology
  • Hippocampus / cytology
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Interneurons / drug effects
  • Interneurons / physiology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Neural Inhibition / physiology*
  • Neurokinin A / analogs & derivatives*
  • Neurokinin A / pharmacology
  • Neurokinin-1 Receptor Antagonists
  • Neuropeptides / physiology*
  • Patch-Clamp Techniques
  • Peptide Fragments / pharmacology
  • Piperidines / pharmacology
  • Quinuclidines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Neurokinin-1 / agonists
  • Receptors, Neurokinin-1 / physiology
  • Substance P / analogs & derivatives*
  • Substance P / pharmacology
  • Synaptic Transmission / physiology*
  • Tachykinins / physiology*
  • Time Factors


  • Excitatory Amino Acid Antagonists
  • GABA Antagonists
  • Neurokinin-1 Receptor Antagonists
  • Neuropeptides
  • Peptide Fragments
  • Piperidines
  • Quinuclidines
  • Receptors, Neurokinin-1
  • Tachykinins
  • senktide
  • neurokinin A (4-10), beta-Ala(8)-
  • SR 140333
  • Substance P
  • Neurokinin A
  • Bicuculline