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Interaction between ephrin/Eph and BDNF in modulating hippocampal synaptic transmission and synapse formation
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Title
Interaction between ephrin/Eph and BDNF in modulating hippocampal synaptic transmission and synapse formation
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Bi
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Caixia
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Caixia Bi
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author
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Plummer
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Mark
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Advisory Committee
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Mark R Plummer
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chair
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Davis
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Robin
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Robin L Davis
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Zhou
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Renping
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Advisory Committee
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Renping Zhou
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Lee
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Francis
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Advisory Committee
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Francis S Lee
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Rutgers University
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Graduate School - New Brunswick
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theses
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2008
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2008-10
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English
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electronic
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x, 113 pages
Abstract
The hippocampus is a brain structure known to be critical for learning and memory consolidation. Abnormal development or damage to this structure is known to play a role in developmental or degenerative neurological disorders such as autism and Alzheimer's disease. In this thesis, I argue that an interaction between ephrin/Eph and BDNF signaling pathways is critical for the development of the selective connection of CA3 neurons to CA1 neurons in hippocampus. This claim was evaluated on the basis of electrophysiology evidence about the ephrin/Eph -- BDNF interaction in synaptic activity, and the effect of the interrupting Eph and BDNF signaling on the hippocampal projection specificity onto CA1 neurons by functional synapse identification via the combination of electrophysiology and immunocytochemistry.
First, I confirmed that the primary hippocampal neuronal culture can be a model for studying the specificity of synaptic connection within the hippocampal circuitry. Functional synapses were characterized by recording from pairs of cells which we subsequently identified with immunocytochemical labeling. Most connections were unidirectional, and I found that when one of the cells was a CA1 neuron (identified by labeling with the CA1 marker anti-SCIP) it was predominantly the postsynaptic member of the pair, a result consistent with in vivo connectivity. Second, ephrin-A/EphA signaling was shown to produce a transient increase in synaptic transmission and be able to inhibit the effect of subsequent BDNF application on synaptic activity. These electrophysiological experiments were suggestive of possible interaction between ephrin-A/EphA and BDNF in modulation synapse formation. Third, interruption of the endogenous EphA signaling by the kinase dominant negative EphA constructs significantly changed the natural synaptic connection selectivity in the hippocampal circuitry and dramatically increased the bi-directional connections in the culture as a consequence.
The empirical results presented in this thesis provide a valuable mechanism for hippocampal trisynaptic circuitry development and function through balancing opposite influences of various modulating factors at specific developmental phases.
First, I confirmed that the primary hippocampal neuronal culture can be a model for studying the specificity of synaptic connection within the hippocampal circuitry. Functional synapses were characterized by recording from pairs of cells which we subsequently identified with immunocytochemical labeling. Most connections were unidirectional, and I found that when one of the cells was a CA1 neuron (identified by labeling with the CA1 marker anti-SCIP) it was predominantly the postsynaptic member of the pair, a result consistent with in vivo connectivity. Second, ephrin-A/EphA signaling was shown to produce a transient increase in synaptic transmission and be able to inhibit the effect of subsequent BDNF application on synaptic activity. These electrophysiological experiments were suggestive of possible interaction between ephrin-A/EphA and BDNF in modulation synapse formation. Third, interruption of the endogenous EphA signaling by the kinase dominant negative EphA constructs significantly changed the natural synaptic connection selectivity in the hippocampal circuitry and dramatically increased the bi-directional connections in the culture as a consequence.
The empirical results presented in this thesis provide a valuable mechanism for hippocampal trisynaptic circuitry development and function through balancing opposite influences of various modulating factors at specific developmental phases.
Note
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Ph.D.
Note
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Includes bibliographical references (p. 94-112).
Subject
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Topic
Neuroscience
Subject
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Topic
Hippocampus (Brain)
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Topic
Neural transmission
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Graduate School - New Brunswick Electronic Theses and Dissertations
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http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.17436
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doi:10.7282/T3B27VMZ
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ETD doctoral
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Open
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Caixia Bi
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Rutgers University. Graduate School - New Brunswick
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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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