Genomic Approaches to Identifying Transcriptional Targets of AP-1, CREB and JNK Signaling in the Nervous System of Drosophila melanogaster

Persistent Link:
http://hdl.handle.net/10150/195739
Title:
Genomic Approaches to Identifying Transcriptional Targets of AP-1, CREB and JNK Signaling in the Nervous System of Drosophila melanogaster
Author:
Etter, Paul Dezso
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:
Although a few regulators of memory and addiction have been identified, the biochemical pathways that mediate the development of addiction and memory remain poorly understood. In addition, important questions remain as to how these two phenomena can persist for so long, sometimes for the entire life of an individual.Signaling molecules and transcription factors are activated in response to stimuli that induce long-term neuronal plastic changes. The transcription factor CREB (cAMP-responsive element binding protein) is clearly involved in triggering processes of addiction and memory, but its sustained activation following a course of chronic drug exposure (or learning) returns to baseline within days [1]. Even the enduring increased levels of deltaFosB (a Fos family transcription factor that couples with other proteins in the AP-1 family to form transcriptional activator/repressor complexes) observed in regions of the mammalian brain following chronic drug exposure, persists for only weeks or months. Thus, although CREB and deltaFosB probably initiate the very stable behavioral changes seen with addiction and memory, their alterations cannot mediate those behavioral changes per se [1]. Long-term up- or down-regulation of molecules downstream of these transcription factors, or others, must be responsible for the enduring modifications in synaptic connectivity and structure believed to be required for the maintenance of these durable behavioral states [2].Many believe that more rapid progress will be made toward understanding the molecular basis of addiction if research efforts proceed hand-in-hand with, rather than in isolation from, the overlapping neurobiological study of learning and memory [1, 2]. The importance and utility of using simple model systems such as Drosophila and Aplysia to identify and characterize genes involved in long-term synaptic plasticity, and hence memory formation, is well documented [3-5]. Identification and functional analyses of neuronal genes transcriptionally regulated by AP-1 and CREB in Drosophila would elaborate on molecular mechanisms of long-term plasticity and hence help us understand, and perhaps manipulate, processes that underlie addiction and memory.
Type:
text; Electronic Dissertation
Keywords:
Molecular & Cellular Biology
Degree Name:
PhD
Degree Level:
doctoral
Degree Program:
Molecular & Cellular Biology; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Ramaswami, Mani
Committee Chair:
Ramaswami, Mani

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titleGenomic Approaches to Identifying Transcriptional Targets of AP-1, CREB and JNK Signaling in the Nervous System of Drosophila melanogasteren_US
dc.creatorEtter, Paul Dezsoen_US
dc.contributor.authorEtter, Paul Dezsoen_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.abstractAlthough a few regulators of memory and addiction have been identified, the biochemical pathways that mediate the development of addiction and memory remain poorly understood. In addition, important questions remain as to how these two phenomena can persist for so long, sometimes for the entire life of an individual.Signaling molecules and transcription factors are activated in response to stimuli that induce long-term neuronal plastic changes. The transcription factor CREB (cAMP-responsive element binding protein) is clearly involved in triggering processes of addiction and memory, but its sustained activation following a course of chronic drug exposure (or learning) returns to baseline within days [1]. Even the enduring increased levels of deltaFosB (a Fos family transcription factor that couples with other proteins in the AP-1 family to form transcriptional activator/repressor complexes) observed in regions of the mammalian brain following chronic drug exposure, persists for only weeks or months. Thus, although CREB and deltaFosB probably initiate the very stable behavioral changes seen with addiction and memory, their alterations cannot mediate those behavioral changes per se [1]. Long-term up- or down-regulation of molecules downstream of these transcription factors, or others, must be responsible for the enduring modifications in synaptic connectivity and structure believed to be required for the maintenance of these durable behavioral states [2].Many believe that more rapid progress will be made toward understanding the molecular basis of addiction if research efforts proceed hand-in-hand with, rather than in isolation from, the overlapping neurobiological study of learning and memory [1, 2]. The importance and utility of using simple model systems such as Drosophila and Aplysia to identify and characterize genes involved in long-term synaptic plasticity, and hence memory formation, is well documented [3-5]. Identification and functional analyses of neuronal genes transcriptionally regulated by AP-1 and CREB in Drosophila would elaborate on molecular mechanisms of long-term plasticity and hence help us understand, and perhaps manipulate, processes that underlie addiction and memory.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectMolecular & Cellular Biologyen_US
thesis.degree.namePhDen_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineMolecular & Cellular Biologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorRamaswami, Manien_US
dc.contributor.chairRamaswami, Manien_US
dc.contributor.committeememberLevine, Richarden_US
dc.contributor.committeememberNagy, Lisaen_US
dc.contributor.committeememberNighorn, Alanen_US
dc.contributor.committeememberParker, Royen_US
dc.identifier.proquest1365en_US
dc.identifier.oclc137355266en_US
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