Long-lasting synaptic facilitation induced by serotonin in superficial dorsal horn neurones of the rat spinal cord

J Physiol. 1996 May 1;492 ( Pt 3)(Pt 3):867-76. doi: 10.1113/jphysiol.1996.sp021352.

Abstract

1. Modulatory actions of serotonin (5-hydroxytryptamine, 5-HT) on excitatory postsynaptic currents (EPSCs) were studied with whole-cell recordings from superficial dorsal horn (SDH) neurones in neonatal rat spinal cord slices. In one-third of SDH neurones, 5-HT induced a sustained potentiation of evoked EPSCs lasting for more than 30 min after wash-out. This potentiation was often preceded by a transient suppression of EPSCs. 2. Serotonin differentially modulated the frequency of miniature EPSCs recorded in the presence of tetrodotoxin (TTX) according to the SDH neurones, producing a transient suppression, a transient facilitation or a long-lasting facilitation. 3. The 5-HT1A-receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) suppressed the amplitude of evoked EPSCs and frequency of miniature EPSCs in a reversible manner. In contrast, the 5-HT2-receptor agonists 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and alpha-methyl-5-HT induced long-lasting potentiations of EPSC amplitude and miniature EPSC frequency. 4. Neither the mean amplitude nor the kinetics of miniature EPSCs were affected by 5-HT during the sustained facilitation of miniature EPSC frequency, suggesting that the facilitatory effect of 5-HT was presynaptically mediated. The 5-HT-induced long-lasting facilitation of miniature EPSC frequency was observed also in Ca(2+)-free, Mg2+ solution. 5. The long-lasting facilitation of evoked EPSC amplitude and miniature EPSC frequency by 5-HT was mimicked by the phorbol ester, phorbol 12,13-dibutyrate (PDBu), and blocked reversibly by the protein kinase C (PKC) inhibitor, calphostin C. Forskolin applied together with 3-isobutyl-1-methylxanthine (IBMX) had no effect on the evoked EPSCs. 6. We conclude that serotonin can induce a long-lasting facilitation of evoked EPSCs and spontaneous release of excitatory transmitter at SDH synapses of rat spinal cord. Our results suggest that intracellular PKC linked to the 5-HT2 receptor may mediate this effect by directly activating the exocytotic machinery.

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Amphetamines / pharmacology
  • Animals
  • Colforsin / pharmacology
  • Electrophysiology
  • Naphthalenes / pharmacology
  • Neurons / metabolism
  • Patch-Clamp Techniques
  • Phorbol Esters / pharmacology
  • Protein Kinase C / antagonists & inhibitors
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / metabolism
  • Receptors, Serotonin, 5-HT1
  • Serotonin / analogs & derivatives
  • Serotonin / pharmacology*
  • Serotonin Receptor Agonists / pharmacology
  • Spinal Cord / drug effects*
  • Synapses / drug effects*
  • Synapses / physiology*
  • Tetrodotoxin / pharmacology

Substances

  • Amphetamines
  • Naphthalenes
  • Phorbol Esters
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Receptor Agonists
  • Colforsin
  • alpha-methylserotonin
  • Serotonin
  • Tetrodotoxin
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Protein Kinase C
  • calphostin C
  • 4-iodo-2,5-dimethoxyphenylisopropylamine
  • 1-Methyl-3-isobutylxanthine