There is extensive research regarding the neural mechanisms that control satiety and meal termination; in contrast, there is very limited understanding of how the central nervous system regulates meal onset and thus the duration of the postprandial intermeal interval (ppIMI) and meal frequency. Based on emerging evidence, we hypothesize that dorsal hippocampal neurons, which are critical for episodic memory, form a memory of a meal and inhibit meal onset during the ppIMI. To test whether hippocampal neurons form a memory of a meal, we first determined that ingesting sucrose or isopreferred concentrations of the non-caloric sweetener saccharin increased the expression of the plasticity-related immediate early gene activity-regulated cytoskeleton-associated protein (Arc) in dorsal CA1 hippocampal (dCA1) neurons in Sprague-Dawley rats. Furthermore, repeated exposure to the sucrose meal attenuated the ability of the sucrose to induce Arc expression. Together, these data indicate that orosensory stimulation produced by a sweet taste is sufficient to induce synaptic plasticity in dCA1 neurons in an experience-dependent manner. Second, we showed that reversibly inactivating dorsal hippocampal neurons with infusions of the GABAA agonist muscimol after the end of a sucrose meal accelerated the onset of the next meal, indicating that dorsal hippocampal neurons inhibit meal onset. Lastly, using a clinically-relevant animal model of early life inflammatory injury, we found that neonatal injury (1) impairs hippocampal-dependent memory, (2) decreases the ppIMI and increases sucrose intake, (3) increases body mass, (4) attenuates sucrose-induced Arc expression in dCA1 neurons, and that (5) blocking inflammatory pain with morphine at the time of injury reverses the effects of injury on memory, energy intake and Arc expression. Collectively, the findings of this dissertation support the overarching hypothesis that dorsal hippocampal neurons inhibit meal onset during the ppIMI and suggest that dorsal hippocampal dysfunction may contribute to the development and/or maintenance of diet-induced obesity.
| Identifer | oai:union.ndltd.org:GEORGIA/oai:scholarworks.gsu.edu:neurosci_diss-1015 |
| Date | 11 May 2015 |
| Creators | Ogawa Henderson, Yoko |
| Publisher | ScholarWorks @ Georgia State University |
| Source Sets | Georgia State University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Neuroscience Institute Dissertations |
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