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Neuromodulation of heterosynaptic plasticity in mouse hippocampus Open Access

Descriptions

Other title
Subject/Keyword
hippocampus
synaptic plasticity
long-term potentiation
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Connor, Steven
Supervisor and department
Nguyen, Peter (Physiology)
Examining committee member and department
Todd, Kathryn (Neuroscience)
Funk, Greg (Physiology)
Ali, Declan (Biological Sciences)
Bains, Jaideep (Neuroscience)
Department
Centre for Neuroscience
Specialization

Date accepted
2011-09-06T15:05:29Z
Graduation date
2011-11
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
The ability of synapses to undergo lasting changes in synaptic strength is considered the primary cellular mechanism for associative memory formation in the mammalian brain. Synapses in the hippocampus, a brain structure required for new memory genesis, exhibit a remarkable capacity for activity-dependent modification known as "synaptic plasticity". Our understanding of the neurobiological correlates of learning and memory has been significantly advanced through the study of one particular form of hippocampal synaptic plasticity known as long-term potentiation (LTP). As LTP has been linked to long-term memory formation, characterizing the mechanisms through which synaptic plasticity is regulated is crucial for advancing our understanding of the brains ability to encode and store information. Hippocampal synaptic plasticity and long-term memory can both be enhanced through activation of neuromodulatory receptors. Noradrenaline is an endogenous neuromodulatory transmitter which is secreted in response to novelty and arousing experiences. Neuromodulatory receptor stimulation can influence synaptic plasticity in a cell-wide manner known as heterosynaptic plasticity. Beta-adrenergic receptor (β-AR) stimulation results in the engagement of downstream signaling cascades capable of augmenting synaptic function. The present thesis identifies mechanisms through which β-ARs enhance heterosynaptic plasticity using electrophysiological recording methods in mouse hippocampal slices. I found that inducing homosynaptic LTP by pairing high-frequency stimulation with beta-adrenergic receptor activation lowered the threshold for heterosynaptic LTP. This form of heterosynaptic plasticity was altered in a mouse model of Fragile X Syndrome (FXS) which was the basis for my second project. When beta-adrenergic receptor-dependent LTP was induced in hippocampal slices from Fragile X mental retardation knockout mice, heterosynaptic LTP was enhanced relative to wild-type littermate controls. My final project investigated the mechanisms through which β-ARs and muscarinic receptors synergistically regulate synaptic plasticity. Co-application of beta-adrenergic and muscarinic receptor agonists enhanced LTP induced by a low-frequency stimulation protocol (5 Hz, 5 s). This form of LTP requires extracellular signal-regulated kinase and protein synthesis. Thus, I was able to further characterize how different neuromodulatory receptors can co-facilitate the induction of enduring synaptic plasticity which is considered the cellular basis for formation of new memories
Language
English
DOI
doi:10.7939/R3XM8G
Rights
License granted by Steve Connor (saconnor@ualberta.ca) on 2011-09-01T15:41:39Z (GMT): Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of the above terms. The author reserves all other publication and other rights in association with the copyright in the thesis, and except as herein provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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