Acute activation of conserved synaptic signaling pathways in Drosophila melanogaster

Persistent Link:
http://hdl.handle.net/10150/280707
Title:
Acute activation of conserved synaptic signaling pathways in Drosophila melanogaster
Author:
Hoeffer Jr., Charles Albert
Issue Date:
2005
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Studies of memory have identified several memory classifications: declarative, implicit, working, and anesthesia-resistant. One simple classification that may be applied to the array of model systems now used to explore memory is the requirement for de novo gene expression and protein synthesis for the formation of long-term memory (LTM). Short-term memory (STM) appears to require the modification of pre-existing neuronal molecules and is resistant to inhibitors of protein synthesis. These molecules, believed to encode proteins that effect long-lasting neuronal changes likely at the level of the synapse, are manifested behaviorally as memory. Neural activity regulates the cellular decision to synthesize these molecules, yet the identity and function of these molecules are largely unknown. What is known has largely been elucidated by work in mollusks and vertebrates in which procedures have been developed to generate neural activity sufficient to induce long-lasting, protein synthesis-dependent neuronal plasticity. Using these procedures, several key intracellular signaling pathways (Ras/ERK, cAMP/PKA) and important early gene products (arc, zif268, AP1) critical to memory have been identified. Similar procedures are not presently available in Drosophila. Establishing these procedures would greatly enhance the Drosophila model system for identification of plasticity molecules and mechanisms that control their expression. We have explored the potential of conditional Drosophila seizure mutants of comatose and CaP60A mutants for the development of a neural activity generation paradigm capable of (1) inducing long lasting and robust neural activity; (2) acute and persistent activation of the ERK signaling pathway and induction of Drosophila homologs of immediate early genes known to be involved in plasticity; (3) alteration of synaptic localization of fasciclin II, a known effector of synaptic plasticity. Using these mutants, we have established the conservation in insects of a known neural activity regulated signaling pathway shown to be critical to both long term plasticity and memory. Secondly, we have identified a central role for AP1, a classical activity induced gene, in regulating Drosophila neural plasticity. The neural activity paradigm coupled with the identification AP1 dual control of both major branches of long term neuronal change, structural and functional plasticity, provides researchers valuable tools for addressing some the outstanding questions facing the plasticity field today.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Biology, Molecular.; Biology, Neuroscience.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Biochemistry and Molecular Cellular Biology
Degree Grantor:
University of Arizona
Advisor:
Ramaswami, Mani

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleAcute activation of conserved synaptic signaling pathways in Drosophila melanogasteren_US
dc.creatorHoeffer Jr., Charles Alberten_US
dc.contributor.authorHoeffer Jr., Charles Alberten_US
dc.date.issued2005en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractStudies of memory have identified several memory classifications: declarative, implicit, working, and anesthesia-resistant. One simple classification that may be applied to the array of model systems now used to explore memory is the requirement for de novo gene expression and protein synthesis for the formation of long-term memory (LTM). Short-term memory (STM) appears to require the modification of pre-existing neuronal molecules and is resistant to inhibitors of protein synthesis. These molecules, believed to encode proteins that effect long-lasting neuronal changes likely at the level of the synapse, are manifested behaviorally as memory. Neural activity regulates the cellular decision to synthesize these molecules, yet the identity and function of these molecules are largely unknown. What is known has largely been elucidated by work in mollusks and vertebrates in which procedures have been developed to generate neural activity sufficient to induce long-lasting, protein synthesis-dependent neuronal plasticity. Using these procedures, several key intracellular signaling pathways (Ras/ERK, cAMP/PKA) and important early gene products (arc, zif268, AP1) critical to memory have been identified. Similar procedures are not presently available in Drosophila. Establishing these procedures would greatly enhance the Drosophila model system for identification of plasticity molecules and mechanisms that control their expression. We have explored the potential of conditional Drosophila seizure mutants of comatose and CaP60A mutants for the development of a neural activity generation paradigm capable of (1) inducing long lasting and robust neural activity; (2) acute and persistent activation of the ERK signaling pathway and induction of Drosophila homologs of immediate early genes known to be involved in plasticity; (3) alteration of synaptic localization of fasciclin II, a known effector of synaptic plasticity. Using these mutants, we have established the conservation in insects of a known neural activity regulated signaling pathway shown to be critical to both long term plasticity and memory. Secondly, we have identified a central role for AP1, a classical activity induced gene, in regulating Drosophila neural plasticity. The neural activity paradigm coupled with the identification AP1 dual control of both major branches of long term neuronal change, structural and functional plasticity, provides researchers valuable tools for addressing some the outstanding questions facing the plasticity field today.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectBiology, Molecular.en_US
dc.subjectBiology, Neuroscience.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineBiochemistry and Molecular Cellular Biologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorRamaswami, Manien_US
dc.identifier.proquest3158104en_US
dc.identifier.bibrecord.b48137479en_US
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