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

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dc.contributor.advisor Young, Paul en
dc.contributor.author Heimer-McGinn, Victoria
dc.date.accessioned 2013-10-14T11:00:27Z
dc.date.available 2014-10-15T04:00:05Z
dc.date.issued 2013
dc.date.submitted 2013
dc.identifier.citation Heimer-McGinn, V. 2013. Development and characterization of novel transgenic techniques for the study of neuronal circuitry. PhD Thesis, University College Cork. en
dc.identifier.endpage 164
dc.identifier.uri http://hdl.handle.net/10468/1251
dc.description.abstract Modern 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.sponsorship Science Foundation Ireland (08/RFP/NSC1381) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2013, Victoria Heimer-McGinn. en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/ en
dc.subject Activity-dependent competition en
dc.subject Neuronal circuits en
dc.subject Tetanus toxin en
dc.subject Dendritic spines en
dc.subject Transgenic mouse models en
dc.subject.lcsh Transgenic mice en
dc.subject.lcsh Molecular neurobiology en
dc.subject.lcsh Microbial toxins en
dc.title Development and characterization of novel transgenic techniques for the study of neuronal circuitry en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD (Science) en
dc.internal.availability Full text available en
dc.description.version Accepted Version
dc.contributor.funder Science Foundation Ireland en
dc.description.status Not peer reviewed en
dc.internal.school Biochemistry en
dc.check.reason This thesis is due for publication or the author is actively seeking to publish this material en
dc.check.opt-out Not applicable en
dc.thesis.opt-out false
ucc.workflow.supervisor p.young@ucc.ie
dc.internal.conferring Autumn Conferring 2013 en


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© 2013, Victoria Heimer-McGinn. Except where otherwise noted, this item's license is described as © 2013, Victoria Heimer-McGinn.
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