The high-affinity choline transporter (CHT) supplies the substrate, choline, for the synthesis of acetylcholine (ACh) within cholinergic neurons. Choline uptake mediated by this protein has been studied for over 30 years and many of the regulatory mechanisms governing its function are well characterized. Early studies, as well as more recent investigations, focused on specific populations of cholinergic axons in the brain, namely the cholinergic innervations of cortical, striatal, and hippocampal regions. Details of the expression and subcellular localization of the high-affinity choline transporter within the projections of the pedunculopontine (PPT) and laterodorsal (LDT) tegmental cholinergic neurons have not been examined. The studies described herein compare the cholinergic axons within two limbic regions that are innervated by the ascending projections from these brainstem nuclei. These experiments were designed to characterize: 1) the relative amount and pattern of subcellular localization of the high-affinity choline transporter protein in the axon varicosities of this projection system; 2) the co-expression of the high-affinity choline transporter and the vesicular acetylcholine transporter in these two populations of axon varicosities; and 3) the organization and possible collateralized projections of the cholinergic neurons that provide cholinergic innervation to these regions. The results of these studies indicate that the expression and localization of the high-affinity choline transporter differs only subtly across brain regions innervated by the brainstem tegmental cholinergic neurons, and suggest that these differences may be accounted for by a pattern of specific innervation arising from distinct subsets of pedunculopontine and laterodorsal tegmental cholinergic neurons.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-10072010-152013 |
| Date | 30 January 2011 |
| Creators | Holmstrand, Ericka C. |
| Contributors | Anthony A. Grace, Ph.D., Robert A. Sweet, M.D., Bita Moghaddam, Ph.D., Philip Winn, Ph.D., Susan R. Sesack, Ph.D., J. Patrick Card, Ph.D. |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-10072010-152013/ |
| Rights | restricted, 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 University of Pittsburgh 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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