Neuromodulation of heterosynaptic plasticity in mouse hippocampusReportar como inadecuado




Neuromodulation of heterosynaptic plasticity in mouse hippocampus - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

hippocampus, synaptic plasticity, long-term potentiation

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.





Autor: Connor, Steven

Fuente: https://era.library.ualberta.ca/


Introducción



University of Alberta Neuromodulation of Heterosynaptic Plasticity in Mouse Hippocampus by Steven Aaron Connor A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy Centre for Neuroscience ©Steven Aaron Connor Fall, 2011 Edmonton, Alberta 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 these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the authors prior writ Dedicated to my family for the love and support they have always given me 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 n...





Documentos relacionados