Neuromuscular Junctions in Drosophila
Neuromuscular Junctions in Drosophila

Author:

Publisher: Academic Press

Published: 1999-04-29

Total Pages: 317

ISBN-13: 0080857779

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Neuromuscular Junctions in Drosophila gathers the main contributions that research using the fruit fly Drosophila melanogaster has made in the area of synapse development, synapse physiology, and excitability of muscles and nerve cells. The chapters in this book represent a synthesis of major advances in our understanding of neuronal development and synaptic physiology, which have been obtained using the above approach.This book is directed to the general neuroscience audience: researchers, instructors, graduate students, and advanced undergraduates who are interested in the mechanisms of synapse development and physiology. However, the book will also be a valuable resource for those that use the fruit fly as a model system in their laboratories. Key Features* Synthesizes the genetic approaches used to study synaptic development and function at the neuromuscular junction, using flies as a model system* Covers major recent advances in muscle development, pathfinding, synapse maturation and plasticity, exo- and endocytosis, and ion channel function* Written in clear language that is easily understandable to readers not already familiar with fruit fly research* Includes numerous diagrams and extensive reference lists

The Neurogenetic Analysis of Synaptogenesis and Synaptic Plasticity in Drosophila Melanogaster
The Neurogenetic Analysis of Synaptogenesis and Synaptic Plasticity in Drosophila Melanogaster

Author: Alexandria Augustine Wise

Publisher:

Published: 2012

Total Pages: 228

ISBN-13:

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Both of these pathways play an important role in neuronal development, transmission, learning and memory, and dysfunction. However, their role in modifying synaptic activity remains unclear. Using Drosophila melanogaster as a model, this thesis will elucidate the role of the APC/C and Rugose in synaptic development and plasticity at the neuromuscular junction.

Genetic and Functional Analysis of Synaptic CA2+ Dynamics in Drosophila
Genetic and Functional Analysis of Synaptic CA2+ Dynamics in Drosophila

Author: Xiaomin Xing

Publisher:

Published: 2014

Total Pages: 132

ISBN-13:

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Ca2+ influx is one of the critical events that trigger synaptic vesicular release, and the accumulation of residual free Ca2+ in synapses is also important for activity-dependent synaptic plasticity. Ca2+ imaging with fluorescence indicators (synthetic or genetically encoded) is a powerful approach to monitor Ca2+ levels in neurons and synapses. Although accumulating studies in vertebrate systems have been carried out to demonstrate the role of Ca2+ in synaptic transmission and plasticity, most of these studies rely on pharmacological methods to infer the molecular mechanism, with less emphasis on forward genetic analysis. The Drosophila neuromuscular junction (NMJ) is a powerful neurogenetic platform for studying synaptic transmission, because of the availability of many mutations. However, not many mutations have been analyzed with Ca2+ imaging. Besides, although Genetically Encoded Ca2+ Indicators (GECIs) including GCaMPs are increasingly popular as the tool to identify neuronal circuits activated by certain stimuli or mediating particular behaviors, the physiological and functional interpretation of neuronal Ca2+ transients reported by GECIs remain obscure. By expressing GCaMPs in NMJ synapses, I characterized a spectrum of genetic mutations including sodium channel alleles parats1, parabss1, potassium channel mutations Shaker (ShM, Sh120), Shab3, ether-a-go-go (eag1, eag4pm), and double mutant eag1 Sh120. Drosophila NMJs contain at least three different types of synapses, which include glutamatergic tonic motor synapse type Ib, phasic motor synapse type Is, and modulatory octopaminergic synapse type II. In this study, I found that the ion channel mutations did not uniformly alter the Ca2+ dynamics in type Ib, Is and II synapses.

Short-term and Long-term Control of Synaptic Strength by Light Activatable Glutamate Receptors at the Drosophila Neuromuscular Junction
Short-term and Long-term Control of Synaptic Strength by Light Activatable Glutamate Receptors at the Drosophila Neuromuscular Junction

Author: Grant Kauwe

Publisher:

Published: 2010

Total Pages: 182

ISBN-13:

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Drosophila neuromuscular junctions (NMJs) exhibit structural and physiological homeostasis during larval development in which the number of boutons and the amount of neurotransmitter released increases in coordination with larval muscle size growth. The Bone Morphogenetic Protein (BMP) signaling pathway, including Glass bottom-boat (Gbb), a BMP ligand, and Wishful thinking (Wit), its presynaptic BMP receptor, are important for regulating this homeostatic growth in larvae. Genetic analysis of Gbb suggests it is released as a retrograde signal from the postsynaptic muscle to initiate presynaptic BMP signaling for synaptic growth. However, muscle expression of Gbb fails to rescue synaptic transmission defects in the gbb mutant, which is instead rescued by nervous system expression of Gbb. To resolve this conflicting data and elucidate the role of Gbb at the NMJ, we investigated the expression of Gbb during Drosophila development at the NMJ. We fused EclipiticGFP to Gbb for visualizing its expression pattern at third-instar larval NMJs. Finally, we demonstrate genetic rescue of the gbb mutant with our transgenic line and provide evidence that Gbb released from the muscle may play a role in higher order synapses beyond the NMJ. Development of the larval neuromuscular junction (NMJ) in Drosophila has been well characterized using genetic mutants and advanced imaging methods. However, the time course of activity-dependent changes in synaptic strength at the larval NMJ has not yet been fully investigated. To further understand the time course of synaptic plasticity at the NMJ, we used the Gal4/UAS system to express the Light-Gated Glutamate Receptor (LiGluR) in the muscle to precisely control postsynaptic activity while performing electrophysiological recordings. Our experiments reveal that long-term postsynaptic LiGluR expression during development induces a homeostatic decrease in bouton density and evoked synaptic transmission. With acute activation of LiGluRs, we potentiate synaptic transmission during high frequency stimulation. CamKII activity is required for this enhancement in synaptic strength by rapid LiGluR activation but it is not necessary for the long-term decrease in bouton density. Finally, we provide evidence that suggests the Wit BMP receptor is not required for the rapid potentiation of synaptic transmission but we provide data to possibly implicate cAMP signaling as a downstream mediator of this effect. These results suggest that a transient increase in postsynaptic activity generated by LiGluR activation may produce a rapid retrograde signal that enhances neurotransmitter release.

Genetic Analysis of Synaptic Growth and Neurotoxic Effects of Radiation Exposure During Development in Drosophila Melanogaster
Genetic Analysis of Synaptic Growth and Neurotoxic Effects of Radiation Exposure During Development in Drosophila Melanogaster

Author:

Publisher:

Published: 2015

Total Pages: 218

ISBN-13:

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Drosophila has been used for decades to identify and analyze molecular pathways underlying processes such as neurodevelopment and the innate immune response and for modeling complex diseases. In this thesis, I describe the use of Drosophila in two different projects. The first is characterization of a novel signaling pathway regulating growth of the larval neuromuscular junction. The second is the development of an experimental model to investigate neurotoxic effects of radiation exposure during development. Using the larval neuromuscular junction as a model synapse we have identified the lipocalin GLaz, the ortholog of human Apolipoprotein D (hApoD) as a novel regulator of synaptic growth. We have shown that postsynaptic insulin signaling promotes growth of the presynaptic terminal and that insulin signaling is increased in GLaz mutants. Overexpression of GLaz or hApoD in glia results in NMJ undergrowth, which is suppressed by simultaneously increasing insulin signaling in muscle. These studies uncover a novel role for lipocalins in regulation of synaptic growth and support a model in which GLaz is secreted from glia and antagonizes postsynaptic insulin signaling to restrict NMJ growth. We have also used Drosophila to model the neurotoxic side effects of radiation exposure during development as in the treatment for pediatric central nervous system malignancies. We have shown that many of the side effects observed in human patients treated with radiation during development can be modeled in Drosophila. Adult flies exposed to radiation during larval development display reduced survival to adulthood, early death, impaired locomotor behavior, and neurodegeneration. These phenotypes are consistent with premature aging. One hallmark of premature aging is chronic inflammation. Similarly, we find persistent activation of the innate immune system in adult flies that were exposed to radiation during larval development. We further demonstrate that the innate immune response is protective acutely following radiation exposure. Together these data demonstrate that the innate immune pathway is a potential therapeutic target for reducing the side-effects of CRT. The use of this experimental model in genetic screens should facilitate identification of additional radioprotective or radiosensitizing pathways, which may be of further therapeutic value.