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bioRxiv · 10.1101/840470

Presynaptic depression maintains stable synaptic strength in developmentally arrested Drosophila larvae

Dickman, D.·ganetzky, b.·Miller, D.·Perry, S.·Goel, P.
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Abstract

Positive and negative modes of regulation typically constrain synaptic growth and function within narrow physiological ranges. However, it is unclear how synaptic strength is maintained when both pre- and post-synaptic compartments continue to grow beyond stages imposed by typical developmental programs. To address whether and how synapses can adjust to a novel life stage for which they were never molded by evolution, we have characterized synaptic growth, structure and function at the Drosophila neuromuscular junction (NMJ) under conditions where larvae are terminally arrested at the third instar stage. While wild type larvae transition to pupae after 5 days, arrested third instar (ATI) larvae persist for up to 35 days, during which NMJs exhibit extensive overgrowth in muscle size, presynaptic release sites, and postsynaptic glutamate receptors. Remarkably, despite this exuberant growth of both pre- and post-synaptic structures, stable neurotransmission is maintained throughout the ATI lifespan through a potent homeostatic reduction in presynaptic neurotransmitter release. Arrest of the larval stage in stathmin mutants reveals a degree of progressive instability and neurodegeneration that was not apparent during the typical larval period. Hence, during a period of unconstrained synaptic growth through an extended developmental period, a robust and adaptive form of presynaptic homeostatic depression can stabilize neurotransmission. More generally, the ATI manipulation provides an attractive system for studying neurodegeneration and plasticity across longer time scales. SIGNIFICANCE STATEMENTIt is unclear whether and how synapses adjust to a novel life stage for which they were never molded by evolution. We have characterized synaptic plasticity at the Drosophila neuromuscular junction in third instar larvae arrested in development for over 35 days. This approach has revealed that homeostatic depression stabilizes synaptic strength throughout the life of arrested third instars to compensate for excessive pre- and post-synaptic growth. This system also now opens the way for the study of synapses and degeneration over long time scales in this powerful model synapse.

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Dickman, D., ganetzky, b., Miller, D., Perry, S., Goel, P.. 2019-11-13. Presynaptic depression maintains stable synaptic strength in developmentally arrested Drosophila larvae. https://doi.org/10.1101/840470

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