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Ph.D. / Behavioral Neuroscience / The purpose of the research described in this dissertation was to determine the neural circuits involved with baseline ethanol consumption and increases in ethanol consumption seen in our animal model of ethanol dependency (further described below). The brain region of focus was the central extended amygdala (cEA) since this region has been shown to be involved in baseline consumption and self-administration of ethanol in rats (Hyytia & Koob, 1995; Eiler et al., 2002) and the changes in ethanol consumption induced by chronic intermittent ethanol vapor exposure seen in rats and mice (Funk et al., 2006; Finn et al., 2007). To determine if the cEA is involved in these behavioral phenotypes, the components of the cEA were lesioned separately. These components included the lateral posterior portion of the bed nucleus of the stria terminalis (BNSTLP), the central nucleus of the amygdala (CeA) and the nucleus accumbens shell (NAc shell). Chapter 2 illustrates that lesions of the BNSTLP decreased baseline ethanol consumption in a 2 hr limited access procedure, but not in a continuous access procedure. Chapter 3 and chapter 4 illustrate that the CeA and NAc shell are involved in baseline ethanol consumption in a limited access procedure, since lesions of these nuclei decreased ethanol consumption. To determine if these nuclei were involved in increases in ethanol consumption, a murine model of ethanol dependency was used. In this procedure C57BL/6J (B6) mice are first acclimated to a limited access two-bottle choice preference procedure. The access period begins 3 hrs into the dark-cycle and continues for 2 hrs. Once acclimated, mice undergo chronic exposure to and intermittent withdrawal from ethanol vapor. Results from chapter 4 indicate that intermittent vapor exposure, as opposed to continuous ethanol vapor exposure, optimizes the increased ethanol x consumption response. As indicated in chapter 2, 3, and 4, lesions of these three components of the cEA did not block the intermittent ethanol vapor induced increase in ethanol consumption. In chapter 4, to determine the brain regions that activate in response to increases in ethanol consumption, a c-fos immunoreactivity study was carried out. The results suggest that the NAc shell and NAc core are the two main brain regions that activate as a result of ethanol consumption specifically in the mice that have been exposed to the intermittent ethanol vapor exposure that show the increase in ethanol consumption. Thus the results suggest that while the NAc shell activates in response to heightened levels of ethanol consumption, it is not necessary to see this increase in ethanol consumption. Overall, the results from these three chapters suggest that while the components of the cEA are involved in baseline ethanol consumption, and are responsive to changes in ethanol consumption (as was the case with the NAc shell), they are not necessary to see the ethanol vapor induced increase in ethanol consumption. These results have implications for understanding the neural circuitry involved in ethanol dependence.

This dissertation provides the foundations of computer-based automated phenotyping methods for analyzing 3D images of mouse embryos. A group-wise registration technique was utilized and optimized and computerized methods were employed for analysis of 3D MRI images of mouse embryos. The assumption that embryo anatomy is highly conserved among genetically identical specimens was verified. The group-wise registration approach was used to align a group of embryos from the 129S1/SvImJ (129Sv) strain as well as a group of C57BL/6J (C57) embryos. Finally, we shed some light on some of the morphological differences between the 129Sv and C57 strains using automated techniques.

This dissertation provides the foundations of computer-based automated phenotyping methods for analyzing 3D images of mouse embryos. A group-wise registration technique was utilized and optimized and computerized methods were employed for analysis of 3D MRI images of mouse embryos. The assumption that embryo anatomy is highly conserved among genetically identical specimens was verified. The group-wise registration approach was used to align a group of embryos from the 129S1/SvImJ (129Sv) strain as well as a group of C57BL/6J (C57) embryos. Finally, we shed some light on some of the morphological differences between the 129Sv and C57 strains using automated techniques.

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