Calcium-dependent mechanisms involved in presynaptic long-term depression at the hippocampal mossy fibre-CA3 synapse

Long-term potentiation (LTP) and long-term depression (LTD) are induced pre synaptically at the hippocampal mossy fibre-CA3 synapse. Activation of pres ynaptic metabotropic glutamate receptors (mGluRs) is necessary, but not suf ficient for the LTD induction. Using mouse hippocampal slices, we attempted to identify additional presynaptic factors involved in the induction of mo ssy fibre LTD. Suppression of a rise in the presynaptic intracellular Ca2concentration ([Ca2+](i)) with a membrane-permeable Ca2+ chelator, 1,2-bis( 2-aminophenoxy)ethane-N,N,N',N-tetraacetic acid tetraacetoxymethyl ester (B APTA-AM), reduced the magnitude of LTD, whereas an increase in Ca2+ influx induced LTD, suggesting that an elevation of presynaptic [Ca2+](i) is cruci al for the LTD induction. A broad-spectrum protein kinase inhibitor, H-7, b locked LTD without affecting a presynaptic inhibition induced by an mGluR a gonist. Furthermore, LTD was reduced by an inhibitor of calmodulin or Ca2+/ calmodulin-dependent protein kinases. Thus, we conclude that mossy fibre LT D requires an increase in presynaptic [Ca2+](i) and subsequent activation o f Ca2+/calmodulin-dependent protein kinases. Because mossy fibre LTP may al so require a rise in presynaptic [Ca2+](i), bidirectional long-term plastic ity at the mossy fibre synapse is likely to be regulated by presynaptic Ca2 +-dependent processes.