Page 1 |
Save page Remove page | Previous | 1 of 139 | Next |
|
small (250x250 max)
medium (500x500 max)
large ( > 500x500)
Full Resolution
All (PDF)
|
This page
All
Subset |
AN ORCHESTRA OF GLUTAMATE RECEPTORS AND TRANSPORTERS IN
SYNAPTIC TRANSMISSION, PLASTICITY AND EXCITOTOXICITY
by
Wei Xu
______________________________________________________
A Dissertation Presented to the
FACUTY OF THE GRADUATE SCHOOL
UNIVERISTY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Rquirements for the Degree
DOCTOR OF PHILOSOPHY
(NEUROSCIENCE)
May 2008
Copyright 2008 Wei Xu
Object Description
| Title | An orchestra of glutamate receptors and transporters in synaptic transmission, plasticity and excitotoxicity |
| Author | Xu, Wei |
| Author email | weixu@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Neuroscience |
| School | College of Letters, Arts and Sciences |
| Date defended/completed | 2007-11-30 |
| Date submitted | 2008 |
| Restricted until | Unrestricted |
| Date published | 2008-03-24 |
| Advisor (committee chair) | Baudry, Michel |
| Advisor (committee member) |
Thompson, Richard F. Ko, Chien-Ping Johnson, Deborah L. |
| Abstract | Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. Synaptic transmission at glutamatergic synapses mediates and regulates basically all aspects of brain functions. The strength of these synapses is subjected to potentiation and depression and these plastic modifications are plausible candidates for information storage in the brain. Excessive activity at glutamatergic synapses, namely excitotoxicity, occurs in many brain diseases and is a critical factor for neuronal death or degeneration. Therefore, to elucidate the molecular mechanisms underlying glutamatergic transmission, plasticity and excitotoxicity constitutes the first step to understand neuronal information processing, learning, memory and brain diseases.; In my dissertation, I report the results of three independent but closely related studies on synaptic transmission, plasticity and excitotoxicity, respectively. In the first part, I provide evidence that two different glutamate transporters, one involved in storing glutamate into synaptic vesicles for synaptic release and the other one responsible for re-uptake of released glutamate inside cells, physically interact with each other and may cooperate for regulating synaptic transmission. In the second study, I first developed a technique to simultaneously measure presynaptic release of glutamate (by targeting vesicular glutamate transporters) and postsynaptic expression of glutamate receptors. Using this technique, I was able to show the existence of a homeostatic relationship between presynaptic and postsynaptic activities. In the third study, I studied interactions between NMDA type ionotropic glutamate receptors and the Group 1 metabotropic glutamate receptors through calpain-mediated proteolytic processing. I showed that this interaction is a critical step for acute neuronal degeneration in excitotxicity and I therefore developed a neuroprotective method by selectively blocking this process. Together, these studies indicate that coordinated functional interactions between glutamate receptors, transporters and different synaptic structures is critical for normal brain functions, that alterations in these processes might participate in brain diseases and that selective targeting of critical elements may provide therapeutic approaches for brain diseases. |
| Keyword | synaptic transmission; synaptic plasticity; glutamate receptor; transporter |
| 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 |
| Type | texts |
| Legacy record ID | usctheses-m1054 |
| Rights | Xu, Wei |
| 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-Xu-20080324 |
| Archival file | uscthesesreloadpub_Volume17/etd-Xu-20080324.pdf |
Description
| Title | Page 1 |
| Full text | AN ORCHESTRA OF GLUTAMATE RECEPTORS AND TRANSPORTERS IN SYNAPTIC TRANSMISSION, PLASTICITY AND EXCITOTOXICITY by Wei Xu ______________________________________________________ A Dissertation Presented to the FACUTY OF THE GRADUATE SCHOOL UNIVERISTY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Rquirements for the Degree DOCTOR OF PHILOSOPHY (NEUROSCIENCE) May 2008 Copyright 2008 Wei Xu |
Comments
Post a Comment for Page 1
