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

The role of internal calcium stores in the induction of long-term depressio n at GABAergic synapses was investigated in the neonatal rat hippocampus. W hole-cell recordings of CA3 pyramidal neurons were performed on hippocampal slices from neonatal (2-4 d old) rats. In control conditions, tetanic stim ulation (TS) evoked an NMDA-dependent long-term depression of GABA(A) recep tor-mediated postsynaptic responses (LTDGABA-A). LTDGABA-A was prevented wh en the cells were loaded with ruthenium red, a blocker of Ca2+-induced Ca2 release (CICR) stores, whereas loading the cells with heparin, a blocker o f 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 LTDGABA-A only when the TS was preceded by depolarizing pulses that increase intracel lular Ca2+ concentration. When applied in the bath, ryanodine prevented the induction of LTDGABA-A. Altogether, these results suggest that ryanodine a cts as a Ca2+-dependent blocker of CICR stores and that the induction of LT DGABA-A required the activation of both presynaptic and postsynaptic CICR s tores.