Complex motor behaviors enable mammals to adapt to their internal and external environments. The lateral hypothalamic area (LHA) contributes importantly to autonomic and endocrine regulation, behavioral states, and energy balance. Orexin (Orx) neuropeptides, produced exclusively by LHA cells, are crucial in the integration of sleep and arousal. The LHA projects densely to the ventral tegmental area (VTA), a dopamine (DA) region that is essential for modulating goal-directed behaviors. Extensive investigations of reward function implicate the LHA-VTA connectivity, an arrangement not yet characterized in detail at the ultrastructural level. The present research sought to clarify the precise interactions of LHA axons with VTA cells. Considering reported physiological responses of VTA cells to LHA stimulation and Orx actions, we hypothesized that both projections interact heavily with DA and GABA cell groups in the VTA, and that LHA axons provide a predominant inhibitory innervation. We used immunocytochemistry to visualize DA or GABA neurons in combination with 1) tract tracer identification of LHA axons or 2) immunolabeling for Orx. Electron microscopic analysis of the VTA revealed that, while the bulk of LHA and Orx projections pass through the VTA, their connections with DA and GABA neurons are a complementary mixture of excitatory and inhibitory synapses. The details of morphology herein suggest many different mechanisms of signal transmission by which LHA axons might contribute information concerning interoceptive state to the adaptive performance of complex motor behaviors modulated by the VTA.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-08202007-162605 |
| Date | 17 January 2008 |
| Creators | Balcita-Pedicino, Judith Joyce |
| Contributors | Linda Rinaman, PhD, Susan R. Sesack, PhD, Anthony A. Grace, PhD |
| 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-08202007-162605/ |
| 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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