June 2008

Document Type


Degree Name



Dept. of Behavioral Neuroscience


Oregon Health & Science University


Significant advances have been made in our understanding of some of the neural circuits and molecular machinery underlying energy homeostasis, and the central melanocortin system has emerged as a particularly important player in this regard. Improvements in our behavioral measures, however, have not kept up with the molecular tools that have been so important to recent advances in the field. Measurements of cumulative food intake are simply insufficient to capture the complexity of ingestive behavior. This complexity must be properly accounted for if we hope to further illuminate the causal relationships between molecular and behavioral functioning. Meal measures are better suited to this task, and a well-validated method for analyzing meal patterns can make better use of molecular biological data. An important part of this task has been to confront the historical challenges facing research into meal pattern. Perhaps the most serious has been the inability, or at best tremendous difficulty, of comparing results between labs. This is due in part to differences in experimental design. For example, it may be expected that meal patterns of animals given access to a liquid diet will differ from solid diet meals (Strohmayer and Smith, 1987; Ho and Chin, 1988). However, the lack of unanimity for how to define a meal has arguably been the greatest impediment to inter-laboratory comparisons (Geary, 2005). Meal definition determination is a prerequisite for calculating meal parameter values. Different meal definitions will produce different meal pattern results; moreover, different statistical methods have been used to identify the “correct” definition for those studies not resorting to the selection of a more or less arbitrary meal definition. A comprehensive parametric study of meal patterns using mice offers the benefit of opening this field to the rapidly growing number of genetically engineered mouse strains. All of these issues will be the topic of chapter two. Having developed and validated the tools for analyzing meal patterns in mice, I apply them to a concrete research problem in Chapter 3. While novel molecular biological details continue to emerge that illuminate the central melanocortin system’s regulation of energy homeostasis, its effects on the initiation, maintenance and termination of meals remain largely unexplored. I report the results of two studies: first, I identify the meal pattern underlying the hyperphagia seen in mice deficient in neuronal POMC (nPOMCKO), and second, having characterized the aberrant meal pattern of nPOMCKO mice, I test whether the final adult meal pattern is present in 5 to 6 week-old nPOMCKO mice, and whether body weight covaries with meal pattern. Finally, in chapter four I review the major findings, drawing conclusions and suggesting possible implications of the thesis and future directions. The remainder of this chapter, then, is devoted to discussion of the literature and issues underlying the controls of feeding behavior and energy homeostasis.




School of Medicine



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