Development and characterization of novel transgenic techniques for the study of neuronal circuitry

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dc.check.opt-outNot applicableen
dc.check.reasonThis thesis is due for publication or the author is actively seeking to publish this materialen
dc.contributor.advisorYoung, Paulen
dc.contributor.authorHeimer-McGinn, Victoria
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2013-10-14T11:00:27Z
dc.date.available2014-10-15T04:00:05Z
dc.date.issued2013
dc.date.submitted2013
dc.description.abstractModern neuroscience relies heavily on sophisticated tools that allow us to visualize and manipulate cells with precise spatial and temporal control. Transgenic mouse models, for example, can be used to manipulate cellular activity in order to draw conclusions about the molecular events responsible for the development, maintenance and refinement of healthy and/or diseased neuronal circuits. Although it is fairly well established that circuits respond to activity-dependent competition between neurons, we have yet to understand either the mechanisms underlying these events or the higher-order plasticity that synchronizes entire circuits. In this thesis we aimed to develop and characterize transgenic mouse models that can be used to directly address these outstanding biological questions in different ways. We present SLICK-H, a Cre-expressing mouse line that can achieve drug-inducible, widespread, neuron-specific manipulations in vivo. This model is a clear improvement over existing models because of its particularly strong, widespread, and even distribution pattern that can be tightly controlled in the absence of drug induction. We also present SLICK-V::Ptox, a mouse line that, through expression of the tetanus toxin light chain, allows long-term inhibition of neurotransmission in a small subset (<1%) of fluorescently labeled pyramidal cells. This model, which can be used to study how a silenced cell performs in a wildtype environment, greatly facilitates the in vivo study of activity-dependent competition in the mammalian brain. As an initial application we used this model to show that tetanus toxin-expressing CA1 neurons experience a 15% - 19% decrease in apical dendritic spine density. Finally, we also describe the attempt to create additional Cre-driven mouse lines that would allow conditional alteration of neuronal activity either by hyperpolarization or inhibition of neurotransmission. Overall, the models characterized in this thesis expand upon the wealth of tools available that aim to dissect neuronal circuitry by genetically manipulating neurons in vivo.en
dc.description.sponsorshipScience Foundation Ireland (08/RFP/NSC1381)en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.format.mimetypeapplication/pdfen
dc.identifier.citationHeimer-McGinn, V. 2013. Development and characterization of novel transgenic techniques for the study of neuronal circuitry. PhD Thesis, University College Cork.en
dc.identifier.endpage164
dc.identifier.urihttps://hdl.handle.net/10468/1251
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2013, Victoria Heimer-McGinn.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectActivity-dependent competitionen
dc.subjectNeuronal circuitsen
dc.subjectTetanus toxinen
dc.subjectDendritic spinesen
dc.subjectTransgenic mouse modelsen
dc.subject.lcshTransgenic miceen
dc.subject.lcshMolecular neurobiologyen
dc.subject.lcshMicrobial toxinsen
dc.thesis.opt-outfalse
dc.titleDevelopment and characterization of novel transgenic techniques for the study of neuronal circuitryen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD (Science)en
ucc.workflow.supervisorp.young@ucc.ie
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