This is a request for a RSDA level II award. The research investigates the affects of behavioral interactions on neuroendocrine cell functioning. Specifically the candidate will examine the impact of interactions with males on neurons that produce gonadotropin-releasing hormone (GnRH) in the female musk shrew (Suncus murinus). Musk shrews, unlike rodents, have no estrous cycle and most aspects of reproduction are induced by contact with males. Mating causes a dramatic (50%) increase in the numbers of cells that contain gonadotropin-releasing hormone immuno-reactivity (GnRH-ir) in the brain. This change occurs in GnRH-ir cells located in the olfactory bulb and rostral forebrain within 15 minutes after the females are introduced to males. Fifteen hours later significant increases in GnRH peptide content can be measured in the preoptic area, median eminence, and several other brain nuclei. This is accompanied by increased numbers of GnRH-ir cells in most brain regions. Cell numbers and GnRH content throughout the brain continue to increase in animals that do not ovulate, but drop in females that ovulate in response to a single ejaculation. The data suggests that behavior triggers increased production of GnRH peptide in specific cell bodies. This highly plastic and dramatic response of GnRH-containing neurons to specific behavioral cues has never been reported before in a mammal.
The aims of these studies are to characterize the sensory/behavioral inputs that are required to activate GnRH neurons. To accomplish this goal the candidate will conduct a series of behavioral studies and then develop the required new surgical methods to denervate selected sensory input pathways. Once the candidate has specified the cues that affect neuroendocrine functioning the candidate will employ them to determine whether behavior affects the transcription of new genetic messages. She will employ in situ hybridization and immunocytochemistry to accomplish these aims. It is well known that behavioral interactions and emotional state can affect reproductive status. How behaviors actually affect the neurons that control neuroendocrine function is not well understood. The proposed experiments would establish a model to assess the direct impact of behavior on the molecular functioning and expression of cells that regulate reproduction in all mammals via their ability to produce and secrete GnRH. RSDA support will free the candidate from teaching and administrative duties. The release time will be used to acquire new skills in the laboratories of two colleagues that are experts in these areas. The goals of this proposal can only be attained if the candidate received the needed training in modern neurobiological and molecular techniques.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02MH001349-04
Application #
2889862
Study Section
Psychobiology, Behavior, and Neuroscience Review Committee (PBN)
Project Start
1996-09-15
Project End
2001-04-30
Budget Start
1999-05-11
Budget End
2000-04-30
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Virginia
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Kudwa, A E; Harada, N; Honda, S-I et al. (2007) Effects of organisational oestradiol on adult immunoreactive oestrogen receptors (alpha and beta) in the male mouse brain. J Neuroendocrinol 19:767-72
Bodo, Cristian; Rissman, Emilie F (2007) Androgen receptor is essential for sexual differentiation of responses to olfactory cues in mice. Eur J Neurosci 25:2182-90
Kudwa, Andrea E; Boon, Wah C; Simpson, Evan R et al. (2007) Dietary phytoestrogens dampen female sexual behavior in mice with a disrupted aromatase enzyme gene. Behav Neurosci 121:356-61
Smith, Jeremy T; Popa, Simina M; Clifton, Donald K et al. (2006) Kiss1 neurons in the forebrain as central processors for generating the preovulatory luteinizing hormone surge. J Neurosci 26:6687-94
Dominguez-Salazar, E; Shetty, S; Rissman, E F (2006) Rapid neural Fos responses to oestradiol in oestrogen receptor alphabeta double knockout mice. J Neuroendocrinol 18:195-202
Kauffman, Alexander S; Bojkowska, Karolina; Wills, Aileen et al. (2006) Gonadotropin-releasing hormone-II messenger ribonucleic acid and protein content in the mammalian brain are modulated by food intake. Endocrinology 147:5069-77
Kudwa, A E; Michopoulos, V; Gatewood, J D et al. (2006) Roles of estrogen receptors alpha and beta in differentiation of mouse sexual behavior. Neuroscience 138:921-8
Imwalle, D Bradley; Bateman, Heather L; Wills, Aileen et al. (2006) Impairment of spatial learning by estradiol treatment in female mice is attenuated by estradiol exposure during development. Horm Behav 50:693-8
Bodo, Cristian; Kudwa, Andrea E; Rissman, Emilie F (2006) Both estrogen receptor-alpha and -beta are required for sexual differentiation of the anteroventral periventricular area in mice. Endocrinology 147:415-20
Kudwa, Andrea E; Bodo, Cristian; Gustafsson, Jan-Ake et al. (2005) A previously uncharacterized role for estrogen receptor beta: defeminization of male brain and behavior. Proc Natl Acad Sci U S A 102:4608-12

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