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THE ROLES OF CALPAINS AND SIRT1 IN RODENT HIPPOCAMPAL SYNAPTIC
PLASTICITY
by
Maggie Meng-Hsiu Chou
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(NEUROSCIENCE)
August 2011
Copyright 2011 Maggie Meng-Hsiu Chou
Object Description
| Title | The roles of calpains and SIRT1 in rodent hippocampal synaptic plasticity |
| Author | Chou, Maggie Meng-Hsiu |
| Author email | menghsic@usc.edu;maggiechou@ymail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Neuroscience |
| School | College of Letters, Arts And Sciences |
| Date defended/completed | 2011-04-27 |
| Date submitted | 2011-07-26 |
| Date approved | 2011-07-27 |
| Restricted until | 2011-07-27 |
| Date published | 2011-07-27 |
| Advisor (committee chair) | Baudry, Michel |
| Advisor (committee member) |
Swanson, Larry W. Walsh, John P. Dane, Joseph A. |
| Abstract | Learning and memory are important functions shared by the living world. In humans, these two functions are a result of brain plasticity and have been studied extensively in the hippocampus, a forebrain structure residing in the medial temporal lobe. Hippocampus is best known for participating in the formation of episodic memory and for exhibiting a special form of synaptic plasticity − long-term potentiation (LTP). LTP is a long lasting enhancement of synaptic transmission resulting from high frequency stimulation of presynaptic neurons. LTP is widely accepted as a molecular biological mechanism underlying certain types of learning and memory. In this dissertation, I evaluate the roles of two protein families, calpain and sirtuin, in rodent hippocampal LTP and contextual fear conditioning learning, which is a hippocampus-dependent task. Calpain is a calcium-dependent neutral protease and sirtuin is NAD⁺-dependent deacetylase. By using calpastatin (an endogenous calpain inhibitor) knockout and over-expressing mice, as well as viral vector-mediated in vivo shRNA interference targeting two ubiquitous calpain isoforms (μ- and m- calpains) in adult rats, I found that calpains might not be directly implicated in the type of LTP induced by customized theta burst stimuli. On the other hand, different calpain isoform deficiencies led to changes in cell excitability, presynaptic properties and NMDA receptor-mediated synaptic responses. In contrast, SIRT1 (sirtuin-1) knockout mice revealed the indispensable requirement of SIRT1 for normal learning, memory and LTP, while over-expressing SIRT1 in the brain did not substantially affect learning and memory or synaptic plasticity. |
| Keyword | calpain; LTP; sirtuin; learning and memory |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Contributing entity | University of Southern California |
| Rights | Chou, Maggie Meng-Hsiu |
| Physical access | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@dots.usc.edu |
| Archival file | uscthesesreloadpub_Volume71/etd-ChouMaggie-178.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@dots.usc.edu |
| Full text | THE ROLES OF CALPAINS AND SIRT1 IN RODENT HIPPOCAMPAL SYNAPTIC PLASTICITY by Maggie Meng-Hsiu Chou A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (NEUROSCIENCE) August 2011 Copyright 2011 Maggie Meng-Hsiu Chou |
