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Abstract:

The probability of synaptic vesicle fusion following an action potential (Pr) and the capacity to express plasticity vary between distinct synaptic populations. How these intrinsic differences in synaptic release character are molecularly encoded remains largely unknown. Stereotyped differences in Pr and presynaptic plasticity have been demonstrated between a pair of glutamatergic tonic/phasic motoneurons (Ib and Is) that co-innervate the body wall muscles of Drosophila larvae, providing a system to interrogate the underlying mechanisms of synaptic heterogeneity. My thesis work demonstrates intrinsic differences in tonic and phasic release properties are partially established by differential expression of the decoy SNARE, Tomosyn. Optogenetic stimulation of tomosyn null mutants reveals a dramatic ~4-fold increase in evoked release from tonic-like Ib motoneurons with no effect on phasic-like Is release. Further, single active zone release probability mapping demonstrates the baseline difference in Pr between Ib and Is is reversed in tomosyn mutants indicating a role for Tomosyn in establishing tonic/phasic release differences. Ib terminals of tomosyn mutants display a phasic-like inability to sustain release during train stimulation, suggesting Tomosyn expression level may broadly regulate tonic/phasic character. Finally, presynaptic homeostatic potentiation (PHP) is impaired in the absence of Tomosyn, suggesting Tomosyn normally plays a role in increasing presynaptic release when postsynaptic glutamate receptor function is acutely impaired. Together, these data suggest Tomosyn expression enables tonic release in Ib by suppressing Pr, generating a reduced level of synaptic vesicle fusion that can be maintained during stimulus trains and that can accommodate robust PHP. Phasic release dominates when Tomosyn expression is low, enabling high intrinsic Pr in Is at the expense of sustained release and robust potentiation. These data argue Tomosyn contributes to the molecular code that establishes intrinsic synaptic release character and plastic range.