The long range goal of this work is to clarify the cellular and molecular events that underlie hormonal control of the development of sexually dimorphic neural pathways in the mammalian forebrain. Central to this goal is a clear understanding of how steroid hormones influence the development of connections between subpopulations of neurons that control sex specific behaviors and physiological responses. The proposed project will use the connections of the anteroventral periventricular nucleus of the preoptic region (AVPV) as a model system to study how sex steroid hormones specify sexually dimorphic patterns of afferent and efferent connections. The overall hypothesis is that the higher levels of estradiol present in males acts on the AVPV through the estrogen receptor alpha (ERa) during the first few days of life to differentiate its neurons and promote innervation by neurons of the principal nucleus of the bed nuclei of the stria terminalis (BSTp) while at the same time suppressing formation of projections from the AVPV to neuroendocrine neurons. Axonal labeling and histochemical methods, as well as both in vivo and in vitro experimental models, will be used to test this hypothesis.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-MDCN-7 (01))
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Kitt, Cheryl A
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Oregon Health and Science University
Other Domestic Higher Education
United States
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Cooke, Bradley M; Simerly, Richard B (2005) Ontogeny of bidirectional connections between the medial nucleus of the amygdala and the principal bed nucleus of the stria terminalis in the rat. J Comp Neurol 489:42-58
Forger, Nancy G; Rosen, Greta J; Waters, Elizabeth M et al. (2004) Deletion of Bax eliminates sex differences in the mouse forebrain. Proc Natl Acad Sci U S A 101:13666-71
Polston, E K; Gu, G; Simerly, R B (2004) Neurons in the principal nucleus of the bed nuclei of the stria terminalis provide a sexually dimorphic GABAergic input to the anteroventral periventricular nucleus of the hypothalamus. Neuroscience 123:793-803
Bouret, Sebastien G; Draper, Shin J; Simerly, Richard B (2004) Formation of projection pathways from the arcuate nucleus of the hypothalamus to hypothalamic regions implicated in the neural control of feeding behavior in mice. J Neurosci 24:2797-805
Bouret, Sebastien G; Draper, Shin J; Simerly, Richard B (2004) Trophic action of leptin on hypothalamic neurons that regulate feeding. Science 304:108-10
Bouret, Sebastien G; Simerly, Richard B (2004) Minireview: Leptin and development of hypothalamic feeding circuits. Endocrinology 145:2621-6
Polston, Eva K; Simerly, Richard B (2003) Sex-specific patterns of galanin, cholecystokinin, and substance P expression in neurons of the principal bed nucleus of the stria terminalis are differentially reflected within three efferent preoptic pathways in the juvenile rat. J Comp Neurol 465:551-9
Zup, Susan L; Carrier, Heather; Waters, Elizabeth M et al. (2003) Overexpression of bcl-2 reduces sex differences in neuron number in the brain and spinal cord. J Neurosci 23:2357-62
Gu, Guibao; Cornea, Anda; Simerly, Richard B (2003) Sexual differentiation of projections from the principal nucleus of the bed nuclei of the stria terminalis. J Comp Neurol 460:542-62
Simerly, Richard B (2002) Wired for reproduction: organization and development of sexually dimorphic circuits in the mammalian forebrain. Annu Rev Neurosci 25:507-36

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