Activation of presynaptic and postsynaptic ryanodine-sensitive calcium stores is required for the induction of long-term depression at GABAergic synapses in the neonatal rat hippocampus

J Neurosci. 2000 Sep 1;20(17):RC94. doi: 10.1523/JNEUROSCI.20-17-j0002.2000.


The role of internal calcium stores in the induction of long-term depression at GABAergic synapses was investigated in the neonatal rat hippocampus. Whole-cell recordings of CA3 pyramidal neurons were performed on hippocampal slices from neonatal (2-4 d old) rats. In control conditions, tetanic stimulation (TS) evoked an NMDA-dependent long-term depression of GABA(A) receptor-mediated postsynaptic responses (LTD(GABA-A)). LTD(GABA-A) was prevented when the cells were loaded with ruthenium red, a blocker of Ca2+-induced Ca2+ release (CICR) stores, whereas loading the cells with heparin, a blocker of IP3-induced Ca2+ release stores, had no effect. The effects of ryanodine, another compound that interferes with CICR stores, were also investigated. Intracellular injection of ryanodine prevented the induction of LTD(GABA-A) only when the TS was preceded by depolarizing pulses that increase intracellular Ca2+ concentration. When applied in the bath, ryanodine prevented the induction of LTD(GABA-A). Altogether, these results suggest that ryanodine acts as a Ca2+-dependent blocker of CICR stores and that the induction of LTD(GABA-A) required the activation of both presynaptic and postsynaptic CICR stores.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Calcium / metabolism*
  • Coloring Agents / pharmacology
  • Electric Stimulation
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Heparin / pharmacology
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • In Vitro Techniques
  • N-Methylaspartate / metabolism
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Neurons / drug effects
  • Neurons / metabolism
  • Patch-Clamp Techniques
  • Presynaptic Terminals / metabolism
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, GABA-A / metabolism
  • Ruthenium Red / pharmacology
  • Ryanodine / pharmacology*
  • Synapses / drug effects
  • Synapses / metabolism*
  • Time
  • gamma-Aminobutyric Acid / metabolism


  • Coloring Agents
  • Receptors, GABA-A
  • Ruthenium Red
  • Ryanodine
  • gamma-Aminobutyric Acid
  • N-Methylaspartate
  • Heparin
  • Calcium