Synaptic plasticity is proposed to be a molecular mechanism underlying multiple forms of learning. The modulation of synaptic plasticity, therefore, may have profound consequences over behavior and may mediate pathological conditions. This project examined synaptic modulation via the activation of á1-adrenergic receptors (á1-ARs) in the bed nucleus of the stria terminalis (BNST), a brain region involved in reward, addiction and anxiety behaviors. I found that in the BNST, á1-ARs induce a heterosynaptic long term depression (LTD) of excitatory transmission that is maintained postsynaptically and requires the activation of L-type voltage gated calcium channels and the functional desensitization of calcium permeable AMPA receptors. Furthermore, this plasticity is disrupted in both behavioral and genetic models of affective disorders suggesting it may play a role in the pathology of these disorders. These data add to the recent evidence suggesting that the á1-AR may be an excellent target for therapeutic intervention in several affective disorders.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-04012009-105433 |
| Date | 21 April 2009 |
| Creators | McElligott, Zoe Anastasia |
| Contributors | Randy Blakely, Habibeh Khoshbouei, Gregory Mathews, Danny Winder |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu//available/etd-04012009-105433/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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