BEHAVIORAL REGULATION OF NEUROENDOCRINE CELLS

描述（改编自申请人摘要）：这是一份申请

DESCRIPTION (Adapted from applicant's abstract): 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.