In this study, the consequences of synaptic mitochondrial dysfunction are examined in the hippocampal CA1 region of brain slices from young (15 to 20 days) rats using a mitochondrial uncoupler, CCCP. In the presence of 10 muM CCCP or 2 muM CCCP, intracellular recordings in CA1 pyramidal cell showed a decrease in stratum radiatum evoked EPSP-IPSPs but an increase in the frequency of spontaneous EPSPs. The increase in spontaneous EPSPs were prevented with both 5 muM BAPTA-AM (with 1 mM probenecid) or 2 muM CsA. However both these drug failed to reverse the blocking effect of CCCP on the evoked EPSPs-IPSPs. Pretreatment of 1 muM FK506, a calcineurin inhibitor, did not prevent the effect of CCCP on either evoked nor spontaneous neurotransmitter release. Thus CCCP increased the spontaneous neurotransmitter release due to increased cytosolic Ca2+ and CCCP abolished evoked neurotransmitter release which Ca2+ is not solely responsible for.