Date of Award
Doctor of Philosophy
Arshad M. Khan
Over 600 million people worldwide are afflicted with obesity. Obesity is a major public health malady characterized, in part, by increased food intake. Persistent overeating may progress into an addiction akin to drug abuse. Sensorimotor integration may be dysfunctional in persons afflicted with obesity and drug addiction. The paraventricular (PVH) and arcuate (ARH) hypothalamic nuclei, the lateral hypothalamic area (LHA) and the ventral tegmental area (VTA) may function in concert to orchestrate responses that involve both sensory inputs and motor outputs to coordinate feeding and drug seeking behaviors. This Dissertation examines the sensory (ARH), integrative (LHA) and motor (PVH and VTA) neuroanatomical underpinnings that may control components of eating and drug seeking behaviors.
Chapter 1 describes experimental work showing that the ARH and PVH mount cellular responses in association with signals arising from activated hindbrain-originating catecholaminergic (CA) neurons. Ablation of CA afferents projecting to PVH neuroendocrine neurons prevents them from mounting the proper neuroendocrine responses to insulin and related systemic challenges. Further, loss of CA innervation in the PVH also resulted in concomitant reductions in the ARH of CA innervation and insulin-induced neuronal activation, particularly in the medial ARH, where feeding-related neuropeptides are enriched. Chapters 2 and 3 are dedicated to understanding the chemical phenotypes of the LHA that extend their neuronal projections to the VTA and, more broadly, how the hypothalamus and midbrain send connections to the VTA. The chemoarchitectural and connectional data presented in Chapters 2 and 3, respectively, lay the neuroanatomical groundwork for future behavioral and related functional studies for exploring complex motivated behaviors such as eating and drug seeking. Collectively, the PVH, ARH, LHA and VTA are integrating centers in a much larger network that controls the rewarding aspects of food intake and drug seeking behaviors that involve sensory and motor components.
Received from ProQuest
Ellen Margaret Walker
Walker, Ellen Margaret, "Neuroanatomical Studies of Hypothalamic Connections Involving the Midbrain and Hindbrain" (2017). Open Access Theses & Dissertations. 583.