Date of Award

Fall 12-10-2018

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience Institute

First Advisor

Marise B. Parent

Second Advisor

Aaron G. Roseberry

Third Advisor

Daniel N. Cox

Fourth Advisor

Ryan T. LaLumiere

Abstract

The memory of a recently eaten meal provides a record of intake that influences future eating behavior. In humans, impairing the encoding of a meal-related memory increases the amount consumed during the next meal, whereas enhancing the memory of meal decreases the amount consumed during the next feeding bout. The brain regions that mediate these mnemonically-driven effects on energy intake are largely unknown. The aim of this dissertation is to identify whether brain regions critical for memory and the mechanisms that underlie memory formation regulate feeding behaviors. The hypothesis guiding this dissertation is that dorsal hippocampal (dHC) neurons, which are essential for episodic and spatial memory, and ventral hippocampal (vHC) neurons, which are associated with affective and emotional memory, form a meal-related memory during the postprandial period that inhibits future intake. The studies outlined herein used pharmacological and optogenetic methods to inhibit dHC and vHC neurons before, during, or after a sucrose, standard chow and saccharin meal to determine whether and when dHC and vHC neurons are involved in regulating energy intake. The findings show that neural activity in both dHC and vHC neurons during the period following ingestion, when the memory of the meal would be undergoing consolidation, is particularly critical for limiting future intake. To determine if dHC and vHC neurons utilize mechanisms of synaptic plasticity necessary for memory formation to regulate energy intake, experiments in this dissertation also tested whether dHC and vHC regulation of intake required N-methyl-D-aspartate receptors (NMDARs) and activity-regulated cytoskeletal protein (Arc) expression. The results suggested that NMDARs and Arc in vHC but not dHC inhibit future energy intake. Collectively, these findings support the hypothesis that hippocampal neurons form meal-related memories that inhibit future intake and provide a more complete understanding of how the brain controls energy intake. Improving our understanding of how the brain regulates energy intake is essential for developing new interventions to help control diet-induced obesity.

DOI

https://doi.org/10.57709/13428396

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