Investigating the Role of Drosophila Tomosyn in Synaptic Strength and Plasticity

Abstract

Neurotransmission is an adaptation of cellular secretion characterized by precise spatial and temporal regulation of SNARE assembly that occurs at specialized presynaptic subdomains in response to transient calcium influx following an action potential. SV fusion from the presynaptic terminal results in a postsynaptic response that varies in size depending on synaptic strength. Both the postsynaptic and presynaptic terminals contribute to synaptic strength with the postsynaptic terminal regulating its own sensitivity for neurotransmitters by governing receptor field composition, and the presynaptic compartment controlling the probability of SV fusion (Pr) following an action potential. While many postsynaptic mechanisms controlling strength have been described, the presynaptic contribution remains incompletely understood. Chapter 1 describes current models of SNARE assembly and disassembly during cycles of synaptic vesicle release. Each protein described in this chapter provides a potential point of regulation for setting presynaptic strength and modulating presynaptic release during plasticity.

Chapter 2 focuses on the decoy SNARE protein Tomosyn and its role at the Drosophila larval neuromuscular junction (NMJ). Larval muscles are typically co-innervated by two glutamatergic motoneurons (Ib and Is) that show highly stereotyped differences in Pr at rest as well as differential expression of presynaptic homeostatic plasticity (PHP) when glutamate receptor function is impaired. Tonic Ib terminals display moderate initial Pr, robust potentiation, and sustained release during train stimulation whereas phasic Is terminals show high intrinsic Pr, rapid depression, and variable PHP expression. Tomosyn contributes to these differences by suppressing Pr and evoked release from tonic Ib motoneurons without affecting phasic Is release. tomosyn null mutants show phasic-like properties including high intrinsic Pr, enhanced depression, and impaired presynaptic homeostatic potentiation (PHP) suggesting Tomosyn regulates the tonic/phasic character and PHP expression of Drosophila synapses. The results in this chapter argue Tomosyn suppresses Pr at Ib synapses to enable tonic release and robust potentiation. Phasic release dominates when Tomosyn expression is low, contributing to the high intrinsic Pr in MNIs terminals at the expense of sustained release and robust PHP. Chapter 3 outlines future directions that might lend further insight into how Tomosyn regulates presynaptic release.