Download or read book Regulation of Synaptic Plasticity at the Drosophila Larval NMJ written by Maude Warren-Paquin and published by . This book was released on 2008 with total page 184 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book A MicroRNA Cluster Negatively Regulates Synaptic Function at Drosophila Larval Neuromuscular Junction written by Ka Wai Karen Tsang and published by . This book was released on 2009 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book A Genetic Analysis of Synaptic Plasticity at the Neuromuscular Junction in Drosophila written by Sophie Ann Petersen and published by . This book was released on 1998 with total page 252 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Neuromuscular Junctions in Drosophila written by and published by Academic Press. This book was released on 1999-04-29 with total page 317 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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
Download or read book Regulation of Synaptic Structure and Function at the Drosophila Neuromuscular Junction written by Aline Dorret Blunk and published by . This book was released on 2013 with total page 177 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neuronal communication requires a spatially organized synaptic apparatus to coordinate neurotransmitter release from synaptic vesicles and activation of postsynaptic receptors. Structural remodeling of synaptic connections can strengthen neuronal communication and synaptic efficacy during development and behavioral plasticity. Here, I describe experimental approaches that have revealed how the actin cytoskeleton participates in transynaptic signaling to control synapse assembly. I also describe my studies on how regulation of endocytic trafficking controls synaptic growth during neuronal development. To identify regulators of synapse assembly, I carried out a large-scale EMS mutagenesis screen of the second chromosome. From this screen I identified a mutation in actin 57B that disrupts synaptic morphology and presynaptic active zone organization. Actin 57B is one of six actin genes in Drosophila and is expressed in body wall muscle during larval development. The isolated allele harbors a point mutation disrupting a highly conserved amino acid present throughout the actin family. Homozygous mutant larvae show impaired alignment and spacing of presynaptic active zones. Additionally, disruption of the organization of the postsynaptic density is observed, with mislocalization of the Spectrin cytoskeleton and the PSD-homolog Disc-Large. Phallodin staining reveals a severe disruption of postsynaptic actin surrounding presynaptic boutons, with the formation of aberrant large actin swirls. Based on these results, we hypothesize that the loss of a synaptic interaction mediated by actin 57B leads to disruption of postsynaptic cytoskeletal organization and dysregulation of signals required to organize presynaptic active zones. Additionally, I present data that provide new insights into the mechanisms controlling synaptic growth signaling during transit through the endocytic pathway. Nervous Wreck (Nwk) is a presynaptic F-BAR/SH3 protein that regulates synaptic growth signaling in Drosophila. Here, I show that Nwk acts through a physical interaction with Sorting Nexin 16 (SNX16). SNX16 promotes synaptic growth signaling by activated BMP receptors, and live imaging in neurons reveals that SNX16-positive early endosomes undergo transient interactions with Nwkcontaining recycling endosomes. We identify an alternative signal termination pathway in the absence of Snx16 that is controlled by ESCRT-mediated internalization of receptors into the endosomal lumen. Our results define a presynaptic trafficking pathway mediated by SNX116, NWK and the ESCRT complex that functions to control synaptic growth signaling at the interface between endosomal compartments. Together, these experiments have expanded our understanding of the molecular mechanisms that control synaptic growth and assembly, highlighting the role of the postsynaptic actin cytoskeleton and the presynaptic endosomal trafficking pathway as key regulators.
Download or read book Short term and Long term Control of Synaptic Strength by Light Activatable Glutamate Receptors at the Drosophila Neuromuscular Junction written by Grant Kauwe and published by . This book was released on 2010 with total page 182 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Function of KEK 6 and DNT2 in Structural Synaptic Plasticity in Drosophila written by Suzana Ulian Benitez and published by . This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Drosophila nervous system undergoes structural synaptic plasticity, however, the mechanisms that govern such event are little understood. Structural synaptic plasticity in mammals is regulated by the neurotrophin brain derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase full length (TrkB-FL). TrkB-FL has a tyrosine kinase domain (TyrK) intracellularly, that is required for its function in structural synaptic plasticity. Trk receptors have long been sought in Drosophila to verify mechanisms of structural synaptic plasticity, but they have not been found. Later, the Kek receptor family was identified as the kinaseless-Trk homologues in flies (Mandai et al., 2009, Bishop, 2013). Here, I validated that Kek-6 is a neurotrophin receptor for DNT2. DNT2 is a novel retrograde factor at the neuromuscular junction (NMJ), and both DNT2 and Kek-6 regulate structural synaptic plasticity. Kek-6 functions in concert with Toll-6. DNT2 and Kek-6 function upstream of CaMKII and Vap33A at the NMJ synapse. Finally, I show that Kek-6 can regulate intracellular levels of calcium in larval motorneurons. In conclusion, I identified a novel mechanism of structural synaptic plasticity in flies that is independent of a TyrK domain. If there are conserved mechanisms, this may also shed light on how truncated Trks function in the adult mammalian brain.
Download or read book Analysis of Neuropeptide Signaling in the Regulation of Synaptic Growth in Drosophila written by and published by . This book was released on 2012 with total page 129 pages. Available in PDF, EPUB and Kindle. Book excerpt: Synapses are the basic units of neural structure and function. Proper synaptic growth is essential for normal development of the nervous system and its function in mediating complex behaviors such as learning and memory. In my dissertation work, I took a combined approach of genetics, molecular biology and biochemistry to identify genes and molecular pathways that regulate synaptic growth in Drosophila, and discovered neuropeptide signaling as a novel mechanism in this process. Neuropeptides have been known to affect neuronal excitability and the strength of synaptic transmission. However, neuropeptides have not been clearly implicated in synaptic growth and development. Through forward genetics, I discovered a cholecystokinin-like receptor (CCKLR) and its predicted ligand drosulfakinin (DSK), as components of a signaling pathway that strongly promote growth of the Drosophila larval neuromuscular junction (NMJ). Loss-of-function mutations of CCKLR or dsk produce severe NMJ undergrowth, whereas over-expression of CCKLR leads to NMJ overgrowth. Through targeted RNAi expression and transgenic rescue experiments I show that presynaptic expression of CCKLR in motor neurons is necessary and sufficient for regulation of NMJ growth. Through analysis of double mutants, I have dissected the signaling pathway downstream of the receptor. I show that this pathway involves G-protein-dependent stimulation of adenyl cyclase to activate PKA, which in turn activates CREB, the cAMP-response element binding protein. In addition, I demonstrate that DSK activates CCKLR biochemically, and that DSK/CCKLR signaling affects synaptic transmission and larval locomotor behavior. To discover novel genes that interact with the CCKLR-signaling pathway to regulate NMJ growth, I performed a modifier screen using chromosomal deficiencies. This pilot screen has identified several regions on the second and third chromosomes that dominantly enhance or suppress the NMJ phenotype of CCKLR mutants. Intriguingly, a number of neuropeptide signaling molecules were found among the candidate interacting genes. Specifically, I have found that leucokinin (DLK) and leucokinin receptor (LKR) negatively regulate NMJ growth, and strongly interact with CCKLR. The results of the modifier screen suggest that neuropeptide signaling may be a more common mechanism for regulating NMJ growth than previously realized and many of the molecules are yet to be uncovered.
Download or read book Biology of the NMDA Receptor written by Antonius M. VanDongen and published by CRC Press. This book was released on 2008-10-29 with total page 368 pages. Available in PDF, EPUB and Kindle. Book excerpt: The NMDA receptor plays a critical role in the development of the central nervous system and in adult neuroplasticity, learning, and memory. Therefore, it is not surprising that this receptor has been widely studied. However, despite the importance of rhythms for the sustenance of life, this aspect of NMDAR function remains poorly studied. Written
Download or read book DCAF12 Is Required For Synaptic Function and Plasticity at the Drosophila Neuromuscular Junction written by Lilian Adilene Patrón and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: We employed imaging, electrophysiological, and molecular techniques with the genetically tractable model organism Drosophila melanogaster to unravel fundamental biological and genetic underpinnings regulating synaptic function and plasticity. Using a forward genetic screen, we identified mutations in the Drosophila ortholog of a human WD40 repeat-containing protein termed DDB1 and CUL4 associated factor 12 (DCAF12). We show that DCAF12 likely serves as an adaptor protein for the DDB1-Cul4 E3 ubiquitin ligase complex by recruiting specific target proteins for ubiquitination. DCAF12 is expressed in neurons, muscles, and glia. In mitotically active cells such as muscles, DCAF12 is localized to nuclei and co-localizes in distinct foci with CUL4, suggesting that DCAF12 mediates a nuclear role for the CUL4 E3 ubiquitin ligase complex. In neurons, DCAF12 is localized to both cytoplasmic and nuclear compartments of motor neuron cell bodies, where it colocalizes with Cul4 in nuclei. DCAF12 is also expressed at the periactive zone of presynaptic terminals, but does not distinctly associate with DDB1 or Cul4 at this region. Evoked neurotransmitter release at larval NMJs is significantly reduced in DCAF12 mutants. These defects are rescued by presynaptic expression of wild-type DCAF12, demonstrating that DCAF12 is required presynaptically and serves as an important component of the machinery that facilitates evoked release. In addition, our studies show that DCAF12 is required for the differential expression of glutamate receptor subunits at the larval NMJ through transcriptional and post-translational mechanisms. GluRIID subunit mRNA levels and GluRIIA/C/D subunit protein levels are increased at DCAF12 mutant NMJs. Normal GluRIIA subunit levels can be restored by postsynaptic expression of wild-type DCAF12, but not with a truncated DCAF12 protein lacking a nuclear localization signal (∆NLS-DCAF12). Furthermore, DCAF12 overexpression in muscle nuclei reduces synaptic GluRIIA levels, an effect that can be suppressed by removing a copy of Cul4. These data strongly indicate that DCAF12 in muscle nuclei is required for GluRIIA expression and/or function in a Cul4-dependent manner. Moreover, homozygous DCAF12-GluRIIA double mutants show a strong synthetic lethality phenotype, providing further support for the hypothesis that GluRIIA directly or indirectly requires DCAF12. Mutations in glutamate receptors at larval NMJs trigger a retrograde trans-synaptic signal that leads to a compensatory increase in presynaptic release, which precisely restores the normal efficacy of synaptic transmission and muscle excitation. Reducing the gene dosage of DCAF12 by one gene copy suppresses the initiation and maintenance of GluRIIA-mediated synaptic homeostatic potentiation. This block of synaptic homeostatic potentiation can be rescued by presynaptic expression of DCAF12. In our studies, we determined that DCAF12 is critical for 3 distinct synaptic mechanisms: evoked neurotransmitter release, neurotransmitter reception by regulation of GluR subunit composition, and retrograde synaptic homeostatic signaling. Future research will strive to identify presynaptic and postsynaptic protein targets of DCAF12 and the Cul4 E3 ubiquitin ligase complex and the role of ubiquitination in regulating these synaptic processes.
Download or read book Selekcionno geneti eskie issledovanija mnogoletnich trav written by and published by . This book was released on 1980 with total page 133 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Muscles and Their Neural Control written by Graham Hoyle and published by John Wiley & Sons. This book was released on 1983 with total page 712 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neurologie, Muskel, Muskelphysiologie.
Download or read book Dynamic Clamp written by Alain Destexhe and published by Springer Science & Business Media. This book was released on 2009-03-11 with total page 428 pages. Available in PDF, EPUB and Kindle. Book excerpt: Dynamic-clamp is a fascinating electrophysiology technique that consists of merging living neurons with computational models. The dynamic-clamp (also called “conductance injection”) allows experimentalists and theoreticians to challenge neurons (or any other type of cell) with complex conductance stimuli generated by a computer. The technique can be implemented from neural simulation environments and a variety of custom-made or commercial systems. The real-time interaction between the computer and cell also enables the design of recording paradigms with unprecedented accuracy via a computational model of the electrode. Dynamic-Clamp: From Principles to Applications contains contributions from leading researchers in the field, who investigate these paradigms at the cellular or network level, in vivo and in vitro, and in different brain regions and cardiac cells. Topics discussed include the addition of artificially-generated synaptic activity to neurons; adding, amplifying or neutralizing voltage-dependent conductances; creating hybrid networks with real and artificial cells; attaching simulated dendritic tree structures to the living cell; and connecting different neurons. This book will be of interest to experimental biophysicists, neurophysiologists, and cardiac physiologists, as well as theoreticians, engineers, and computational neuroscientists. Graduate and undergraduate students will also find up-to-date coverage of physiological problems and how they are investigated.
Download or read book Fly Pushing written by Ralph J. Greenspan and published by CSHL Press. This book was released on 2004 with total page 212 pages. Available in PDF, EPUB and Kindle. Book excerpt: A second edition of the classic handbook has become a standard in the Drosophila field. This edition is expanded to include topics in which classical genetic strategies have been augmented with new molecular tools. Included are such new techniques as homologous recombination, RNAi, new mapping techniques, and new mosaic marking techniques.
Download or read book Behavioral Genetics of the Fly Drosophila Melanogaster written by Josh Dubnau and published by Cambridge University Press. This book was released on 2014-06-26 with total page 309 pages. Available in PDF, EPUB and Kindle. Book excerpt: A comprehensive portrayal of the behaviour genetics of the fruit fly (Drosophila melanogaster) and the methods used in these studies.
Download or read book Drosophila Neurobiology written by Bing Zhang and published by . This book was released on 2010 with total page 552 pages. Available in PDF, EPUB and Kindle. Book excerpt: Based on Cold Spring Harbor Laboratory's long-running course, "Drosophila Neurobiology: A Laboratory Manual" offers practical advice to all researchers interested in using "Drosophila" as an experimental model for investigating the nervous system.
Download or read book Molecular and Cellular Approaches to Neural Development written by W. Maxwell Cowan and published by Oxford University Press, USA. This book was released on 1997 with total page 575 pages. Available in PDF, EPUB and Kindle. Book excerpt: This text provides a broad but authoritative view of the cellular and molecular aspects of developmental neurobiology written by leaders in the field.
