CALCIUM-DEPENDENT PAIRED-PULSE FACILITATION OF MINIATURE EPSC FREQUENCY ACCOMPANIES DEPRESSION OF EPSCS AT HIPPOCAMPAL SYNAPSES IN CULTURE

Two forms of evoked neurotransmitter release at excitatory synapses be tween cultured hippocampal neurons have been described. After an actio n potential, it has been shown that transmitter initially is released synchronously, and this is followed by a period of ''slow'' asynchrono us release. The ''fast'' synchronous component of release at these syn apses has been found routinely to demonstrate paired-pulse and tetanic depression, whereas the short-term plasticity of asynchronous release has not been investigated. in the present experiments, we have used t he whole-cell patch-clamp technique to record from pairs of neurons in a low-density hippocampal culture preparation to determine both the p roperties and underlying mechanisms of short-term plasticity of asynch ronous release. It was found that an increase in miniature EPSC (mEPSC ) frequency accompanied both single and multiple stimuli, and this mEP SC increase was facilitated during paired stimuli, even when the evoke d synchronous release was depressed. In addition, both the activity-de pendent depression of evoked EPSCs and facilitation of asynchronous mE PSC release were dependent on Ca accumulation in the nerve terminal. H owever, the Ca-dependent mechanisms underlying these two processes cou ld be distinguished by the differential effects of two membrane-permea nt calcium chelators, BAPTA-AM and EGTA-AM. Frequency-dependent depres sion of evoked EP-SCs involves a rapid rise in intraterminal Ca, which likely triggers a process that proceeds in a Ca-independent manner, w hereas the asynchronous release may be linked more directly to a susta ined increase in intraterminal Ca.