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Dissertation
The effects of a neurosteroid, pregnenolone sulfate, in the cerebellum on vestibulo-ocular reflex adaptation (VOR) in goldfish
Doctor of Philosophy (Ph.D.), Drexel University
Jun 2006
DOI:
https://doi.org/10.17918/etd-1119
Abstract
The vestibulo-ocular reflex (VOR) is an evolutionarily well conserved system that stabilizes visual images on the retina during rapid head movement. Adaptation of the VOR has served as a model system for sensori-motor learning and memory, as well as neuroplastic phenomena within the cerebellum. The results presented in this thesis investigated the effects of pregnenolone sulfate (PREGS) on the acquisition (learning) and retention (memory) phases of VOR adaptation. PREGS significantly enhanced the acquisition phase of adaptive VOR gain increases (104% via microdialysis, 101% via microinjection), but not adaptive VOR gain decreases when infused into the cerebellum of goldfish without altering normal operation of this reflex prior to the initiation of adaptive training. In addition, PREGS did not significantly reverse adaptive VOR gain decreases. The summation of these results suggests that the distinct properties of adaptive VOR gain increases and decreases are mediated by different pharmacological mechanisms and/or possibly at different neuronal sites. PREGS did not enhance nor inhibit the retention phase of adaptive VOR gain increases or decreases when infused into the cerebellum of goldfish. These results suggest that these two adaptation tasks (acquisition and retention) could also occur by different pharmacological mechanisms and/or their site of adaptation resides in different anatomical structures (cerebellum for acquisition, vestibular nuclei for retention). In addition, we demonstrated that a cytochrome P-450scc-like protein is present in the cerebellum of goldfish, specifically in the Purkinje cell layer; suggesting that these cells possess the enzyme cytochrome P-450scc and produce pregnenolone and PREGS. This work agrees with earlier studies in which this enzyme specific for the formation of pregnenolone has been detected and localized in the cerebellar Purkinje cells of both higher and lower vertebrates, suggesting that cytochrome P-450scc is a highly conserved protein.
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Details
- Title
- The effects of a neurosteroid, pregnenolone sulfate, in the cerebellum on vestibulo-ocular reflex adaptation (VOR) in goldfish
- Creators
- Michele Margaret Cox - DU
- Contributors
- William Freedman (Advisor) - Drexel University (1970-)James G. McElligott (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University
- Other Identifier
- 1119; 991014632722804721