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The role of brain-derived neurotrophic factor in the regulation of dendritic arbor morphology, neuronal network activity, and neuroprotection
Descriptive
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Title
The role of brain-derived neurotrophic factor in the regulation of dendritic arbor morphology, neuronal network activity, and neuroprotection
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O'Neill
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Kate M.
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1989-
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Kate M. O'Neill
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author
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Firestein
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Bonnie L
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Bonnie L Firestein
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Advisory Committee
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chair
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Shinbrot
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Troy
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Troy Shinbrot
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Advisory Committee
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internal member
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(type = family)
Paradiso
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Ken
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Ken Paradiso
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Advisory Committee
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internal member
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(type = family)
Thakker-Varia
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Smita
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Smita Thakker-Varia
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Advisory Committee
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(authority = RULIB)
internal member
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Morrison, III
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Barclay
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Barclay Morrison, III
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Advisory Committee
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(authority = RULIB)
outside member
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Rutgers University
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degree grantor
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Graduate School - New Brunswick
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theses
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2017
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2017-05
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2017
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xx
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eng
Abstract
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The dendritic architecture of a neuron determines how it receives inputs, and thus, changes in dendrite morphology will affect connectivity among neurons. Aberrant changes in the development of the arbor, or after the arbor has formed, can disrupt the functioning of neural circuits, causing severe brain dysfunction and leading to pathologies seen in cognitive disorders, neurological diseases, and trauma. Brain-derived neurotrophic factor (BDNF) is one of the most well-studied regulators of dendritic and synaptic plasticity. It is also known to be a pro-survival factor and is overexpressed in neurons that survive injuries, such as ischemia. This dissertation explores how BDNF shapes the dendritic arbor of single hippocampal neurons and the dynamics of in vitro hippocampal networks. Previous work in our laboratory has shown that BDNF significantly increases proximal dendrite branching in hippocampal neurons after 72 hours of bath application. Building on this work, we show that local application of BDNF via microbeads increases both proximal and distal dendrite branching in a shorter time than does bath application. We also show that overexpression of BDNF shapes the dendritic arbor differently depending on the intracellular targeting of BDNF transcripts. To understand how BDNF affects the development of hippocampal neuronal networks, we use microelectrode arrays (MEAs) to record the spontaneous activity of these networks before and after bath application of BDNF. Our results suggest a role for BDNF in the long-term development of neuronal network dynamics, as changes in network parameters were only observed at one week after treatment. Finally, we explore whether BDNF exerts neuroprotective effects following excitotoxic injury. Global activity parameters decrease following injury with excess glutamate with no benefit from BDNF treatment, but BDNF does protect connections with distinct baseline synchronizations from injury-induced decreases. Taken together, our results indicate that BDNF is involved in the development of the dendritic arbor, the maturation of neuronal networks, and the protection of distinct connections after excitotoxic injury.
Subject
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Topic
Biomedical Engineering
Subject
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Topic
Neurons
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Rutgers University Electronic Theses and Dissertations
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ETD_7976
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electronic resource
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application/pdf
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1 online resource (xiv, 203 p. : ill.)
Note
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Ph.D.
Note
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Includes bibliographical references
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by Kate M. O’Neill
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Title
Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
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Identifier
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doi:10.7282/T3SQ9395
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(authority = ExL-Esploro)
ETD doctoral
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Rights
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The author owns the copyright to this work.
RightsHolder
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Name
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O'Neill
GivenName
Kate
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M.
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Permission or license
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2017-04-10 15:13:12
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Kate O'Neill
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Rutgers University. Graduate School - New Brunswick
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Author Agreement License
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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2017-05-31
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2019-05-31
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after May 31st, 2019.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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