Presynaptic Substrates Mediating Fos- and Jun-dependent Plasticity at the Drosophila Neuromuscular Junction

Persistent Link:
http://hdl.handle.net/10150/193677
Title:
Presynaptic Substrates Mediating Fos- and Jun-dependent Plasticity at the Drosophila Neuromuscular Junction
Author:
Kim, Susy M.
Issue Date:
2007
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:
Fos and Jun are transcription factors that heterodimerize to form AP-1, a transcriptional activator complex. They are two among many important candidate immediate early genes long hypothesized to function as transcriptional gatekeepers between the short-term and long-term modifications of synaptic efficacy postulated to underlie learning and memory. In normally active Drosophila motor neurons, overexpression of AP-1, induces cAMP- and CREB- dependent forms of synaptic enhancement. The activities of immediate early genes such as fos, jun, and CREB have long been assumed to achieve synaptic enhancement by increasing synapse number. We show that at the Drosophila neuromuscular junction (NMJ), an AP-1- and CREB- dependent form of presynaptic strengthening is mediated by increasing the weights of unitary synapses and not through the insertion of additional release sites. Post-tetanic potentiation (PTP) is reduced at these synapses, suggesting that the mechanisms underlying this short-term form of synaptic enhancement may be stably recruited by pathways activated downstream of AP-1 overexpression. Electrophysiological and FM1-43 based measurements further demonstrate that enhanced neurotransmitter release is accompanied by an increase in the actively cycling synaptic-vesicle pool at the expense of the reserve pool. Increases in both transmitter release and cycling-pool size are blocked under conditions of CREB inhibition arguing that: a) AP-1 and CREB are required for reserve-pool mobilization; and b) that sustained reserve pool mobilization may underlie this form of plasticity. These findings together suggest transcriptional mechanisms believed to participate in long-term forms of synaptic enhancement may, in some instances, be accomplished by the stable recruitment of mechanisms that normally underlie short-term synaptic change.
Type:
text; Electronic Dissertation
Keywords:
Neuroscience
Degree Name:
PhD
Degree Level:
doctoral
Degree Program:
Neuroscience; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Zinsmaier, Konrad E.

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titlePresynaptic Substrates Mediating Fos- and Jun-dependent Plasticity at the Drosophila Neuromuscular Junctionen_US
dc.creatorKim, Susy M.en_US
dc.contributor.authorKim, Susy M.en_US
dc.date.issued2007en_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.abstractFos and Jun are transcription factors that heterodimerize to form AP-1, a transcriptional activator complex. They are two among many important candidate immediate early genes long hypothesized to function as transcriptional gatekeepers between the short-term and long-term modifications of synaptic efficacy postulated to underlie learning and memory. In normally active Drosophila motor neurons, overexpression of AP-1, induces cAMP- and CREB- dependent forms of synaptic enhancement. The activities of immediate early genes such as fos, jun, and CREB have long been assumed to achieve synaptic enhancement by increasing synapse number. We show that at the Drosophila neuromuscular junction (NMJ), an AP-1- and CREB- dependent form of presynaptic strengthening is mediated by increasing the weights of unitary synapses and not through the insertion of additional release sites. Post-tetanic potentiation (PTP) is reduced at these synapses, suggesting that the mechanisms underlying this short-term form of synaptic enhancement may be stably recruited by pathways activated downstream of AP-1 overexpression. Electrophysiological and FM1-43 based measurements further demonstrate that enhanced neurotransmitter release is accompanied by an increase in the actively cycling synaptic-vesicle pool at the expense of the reserve pool. Increases in both transmitter release and cycling-pool size are blocked under conditions of CREB inhibition arguing that: a) AP-1 and CREB are required for reserve-pool mobilization; and b) that sustained reserve pool mobilization may underlie this form of plasticity. These findings together suggest transcriptional mechanisms believed to participate in long-term forms of synaptic enhancement may, in some instances, be accomplished by the stable recruitment of mechanisms that normally underlie short-term synaptic change.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectNeuroscienceen_US
thesis.degree.namePhDen_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineNeuroscienceen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorZinsmaier, Konrad E.en_US
dc.contributor.committeememberGronenberg, Wulfilaen_US
dc.contributor.committeememberNighorn, Alanen_US
dc.contributor.committeememberLevine, Richard B.en_US
dc.identifier.proquest2427en_US
dc.identifier.oclc659748338en_US
All Items in UA Campus Repository are protected by copyright, with all rights reserved, unless otherwise indicated.