EVIDENCE FOR SYNAPTOTAGMIN AS AN INHIBITORY CLAMP ON SYNAPTIC VESICLERELEASE IN APLYSIA NEURONS

While previous studies have demonstrated that synaptotagmin plays an e ssential role in evoked neurotransmitter release, it has been difficul t to determine whether it acts to facilitate or inhibit release. To ad dress this question, we used acute genetic manipulations to alter the expression of synaptotagmin in Aplysia neurons. Transient overexpressi on of synaptotagmin in acutely dissected cholinergic neurons and in cu ltured glutaminergic neurons decreased the amplitude of the excitatory postsynaptic potential (EPSP) by 32% and 26%, respectively. In contra st, treatment of cultured presynaptic neurons with synaptotagmin antis ense oligonucleotides increased the amplitude of the EPSP by 50-75%. T hese results are consistent with a role of synaptotagmin as an inhibit or of release.