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Characterizing the Role of GABA in the Paraventricular Thalamic Nucleus in the Control of Feeding and Body Weight

Abstract

The paraventricular nucleus of the thalamus (PVT) is a midline thalamic nucleus traditionally thought to play a role in nonspecific arousal given its extensive connections throughout the brain. However, there has been a recent emphasis on the role of the PVT in the control of feeding due to its associations with hypothalamic regions that integrate energy states and its projections to amygdala and ventral striatal regions implicated in reward and motivation. The purpose of the current series of experiments was to characterize the role of GABA in the PVT in relation to feeding. An introduction is presented in the first chapter summarizing what is currently known about how the PVT fits into the neurocircuitry governing feeding behavior, from an anatomical and functional point of view. Then, the following questions were addressed: 1) Do GABA receptor subtypes differentially mediate GABA-induced feeding in the PVT? 2) Are there regional differences between the anterior (aPVT) and posterior (pPVT) subregions of the PVT? 3) Do GABA receptors in the PVT play a role in natural feeding? In Chapter 2, the PVT was inhibited by microinjections of the GABAA agonist muscimol or the GABAB agonist baclofen, and food intake was measured. I found that the agonist for both receptor subtypes produced dose-dependent increases in feeding in satiated rats. In Chapter 3, separate groups of rats received stereotaxic implantation of a cannula into either the aPVT or pPVT. While pPVT injections of either muscimol or baclofen elicited eating, the effect of muscimol was reduced while baclofen was ineffective when injected into the aPVT, demonstrating a regionally-specific effect. In Chapter 4, rats were fasted for 24 hr, which produced a large increase in intake upon refeeding. PVT injection of the GABAA antagonist bicuculline suppressed this deprivation-induced feeding, suggesting that GABAA receptors in the PVT may mediate this form of natural feeding. Together, these studies suggest that the PVT, in particular its posterior division, is part of a specialized circuit governing feeding behavior.

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