The development and plasticity of the neuromuscular junction in Drosophila will be studied using mutations that disrupt several aspects of neuronal function. The proposed research will test the hypothesis that neural activity, presumably by alterations in the level of second messengers, is a major factor involved in regulating synaptogenesis. Activity levels will be modified to different extents by mutations affecting ion channels and neurotransmitter release, whereas CAMP levels will be altered by using mutations that affect CAMP metabolic enzymes. We will use immunocytochemical staining of motor axon terminals to determine if changes in the levels of activity of motorneurons or changes in CAMP levels during development generate morphological changes. Ultrastructural reconstructions and macropatch recordings of single synaptic boutons will allow us to assess the structural and functional nature of these changes. We will also determine the sequence of events during larval development that lead to the final pattern of axon terminals, and if there are critical stages of development during which this morphology is amenable to change. We have already found that hyperactivity throughout development leads to morphological and physiological abnormalities at the Drosophila larval neuromuscular junction. The combination of conventional electrophysiological and anatomical techniques, and the powerful genetic and molecular tools developed in Drosophila, should allow us to gain much insight into the mechanisms underlying synaptic plasticity. Furthermore, this study may be valuable for the understanding of neuropathologies that result from abnormal states of neuronal activity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS030072-01
Application #
3417021
Study Section
Neurology C Study Section (NEUC)
Project Start
1992-01-01
Project End
1994-12-31
Budget Start
1992-01-01
Budget End
1992-12-31
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Massachusetts Amherst
Department
Type
Schools of Arts and Sciences
DUNS #
153223151
City
Amherst
State
MA
Country
United States
Zip Code
01003
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Chai, Andrea; Withers, James; Koh, Young Ho et al. (2008) hVAPB, the causative gene of a heterogeneous group of motor neuron diseases in humans, is functionally interchangeable with its Drosophila homologue DVAP-33A at the neuromuscular junction. Hum Mol Genet 17:266-80
Griffith, Leslie C; Budnik, Vivian (2006) Plasticity and second messengers during synapse development. Int Rev Neurobiol 75:237-65
Ruiz-Canada, Catalina; Budnik, Vivian (2006) Introduction on the use of the Drosophila embryonic/larval neuromuscular junction as a model system to study synapse development and function, and a brief summary of pathfinding and target recognition. Int Rev Neurobiol 75:1-31
Ruiz-Canada, Catalina; Budnik, Vivian (2006) Synaptic cytoskeleton at the neuromuscular junction. Int Rev Neurobiol 75:217-36
Mathew, Dennis; Popescu, Andrei; Budnik, Vivian (2003) Drosophila amphiphysin functions during synaptic Fasciclin II membrane cycling. J Neurosci 23:10710-6
Packard, Mary; Mathew, Dennis; Budnik, Vivian (2003) FASt remodeling of synapses in Drosophila. Curr Opin Neurobiol 13:527-34
Koh, Young-Ho; Ruiz-Canada, Catalina; Gorczyca, Michael et al. (2002) The Ras1-mitogen-activated protein kinase signal transduction pathway regulates synaptic plasticity through fasciclin II-mediated cell adhesion. J Neurosci 22:2496-504
Park, Demian; Coleman, Melissa J; Hodge, James J L et al. (2002) Regulation of neuronal excitability in Drosophila by constitutively active CaMKII. J Neurobiol 52:24-42
Thomas, U; Ebitsch, S; Gorczyca, M et al. (2000) Synaptic targeting and localization of discs-large is a stepwise process controlled by different domains of the protein. Curr Biol 10:1108-17

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