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SYNAPSE MAINTENANCE AND FUNCTION AT THE MOUSE
NEUROMUSCULAR JUNCTION: IMPLICATIONS IN DISEASES
by
Ming-Yi Lin
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)
May 2011
Copyright 2011 Ming-Yi Lin
Object Description
| Title | Synapse maintenance and function at the mouse neuromuscular junction: implications in diseases |
| Author | Lin, Ming-Yi |
| Author email | mingyili@usc.edu; mingyilin@gmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Biology (Neurobiology) |
| School | College of Letters, Arts and Sciences |
| Date defended/completed | 2010-11-23 |
| Date submitted | 2011 |
| Restricted until | Unrestricted |
| Date published | 2011-02-22 |
| Advisor (committee chair) | Ko, Chien-Ping |
| Advisor (committee member) |
Chow, Robert Butler, Samantha Youn, Jang |
| Abstract | The synapse is the fundamental building block of the brain circuitry responsible for the human behavior. An understanding of synaptic structure and function is required to elucidate how the brain functions. In this study, we used the neuromuscular junction (NMJ) as a model synapse to investigate the basic mechanisms of synapse function and maintenance.; In chapter 2 of the dissertation, we studied the mechanism of synaptic vesicle release, more specifically, the function of a pre-synaptic protein, complexin, at the NMJ. We found that genetic ablation of complexin caused a reduced and asynchronous vesicle release at the NMJ without changing the NMJ structure. This leads us to propose the hypothesis that complexin may facilitate and synchronize vesicle release by coupling synaptic vesicles with calcium channels.; In chapter 3, we examined whether an increase in post-synaptic muscle size has a retrograde effect on the motoneuron and NMJ. Knockout of myostatin, a negative regulator for muscle growth, results in an increase in muscle and NMJ size. Synaptic transmission was significantly increased in myostatin null mice, maintaining the synaptic homeostasis. The effect of myostatin deletion on motoneuron and NMJ degeneration was also explored in a mouse model of amyotrophic lateral sclerosis (ALS).; Finally, in chapter 4, we investigated the maintenance and function of the NMJ in a mouse model of spinal muscular atrophy (SMA), a childhood motoneuron disease. We found that despite the apparent muscle weakness, NMJs in the hindlimb muscles were innervated and functional, which suggests that the NMJ may not be the cause of hindlimb muscle dysfunction.; Maintaining proper synapse function is critical for the function of the nervous system, and disruption in synaptic structure and function has been implicated in many neurological diseases. The current study provides more understandings on how synapses function and may bring insight into diseases that involve synaptic defects. |
| Keyword | neuromuscular junction; motoneuron; complexin; amyotrophic lateral sclerosis; spinal muscular atrophy; myostatin; muscle |
| 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-m3669 |
| Rights | Lin, Ming-Yi |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-lin-4336 |
| Archival file | uscthesesreloadpub_Volume44/etd-lin-4336.pdf |
Description
| Title | Page 1 |
| Full text | SYNAPSE MAINTENANCE AND FUNCTION AT THE MOUSE NEUROMUSCULAR JUNCTION: IMPLICATIONS IN DISEASES by Ming-Yi Lin 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) May 2011 Copyright 2011 Ming-Yi Lin |
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