NEUROPEPTIDES IN THE CONTROL OF REPRODUCTIVE BEHAVIOR

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DESCRIPTION (adapted from applicant's abstract): The accessory olfactory system (AOS) of the rodent processes chemosensory information concerning gender, reproductive condition, and social status. Signals coming into the AOS are detected by receptor neurons of the vomeronasal organ (VNO), sent to the accessory olfactory bulb (AOB), and subsequently to the hypothalamic pituitary axis to modulate gonadotropin releasing hormone (GnRH) neurons. In the female mouse, male urine and urine-derived compounds have been demonstrated to alter such GnRH-mediated events as puberty acceleration and estrous cyclicity. Urine and urinary compounds also rapidly elevate c-fos mRNA expression in the AOB and directly alter the activity of VNO sensory neurons. The present application will make use of these chemosensory stimulants to study signal processing in the AOB. Three hypotheses constitute the specific aims: 1) Spatial segregation of projections from the VNO to the AOB is anatomically and functionally significant; 2) Periglomerular cells modulate signals arriving at the AOB; 3) Chemosensory signals are encoded within the microcircuitry of the AOB. Neuroanatomical tract-tracing techniques will be used to map the projections from the VNO the AOB. Patterns of cellular activation in the AOB will be examined in female mice of varying physiological states following exposure to urine from males or females of varying physiological states. These studies will define the anatomic structure-function relationship in chemosensory signaling between the VNO and the AOB. Electrophysiological techniques will be applied to study the membrane properties and neurotransmitter responsiveness of isolated AOB cells, monolayered cells in organotypic culture, and cells in a slice preparation. These studies will elucidate the modulatory actions of periglomerular cells on mitral cell activity. Finally, with all circuitry intact, electrophysiological techniques will be applied to the whole animal to compare the effects of chemosensory exposure with those of VN nerve stimulation and assess the influence of pharmacological blockers administered at the VN terminal endings on the activity of mitral cells. The proposed experiments will provide a better understanding of how chemosensory signals are processed and encoded before reaching the GnRH neuron and thus provide insight into GnRH-mediated control of neuroendocrine events. The results may aid in our understanding of the mechanisms underlying cyclicity and fertility in the human female and may direct future efforts in delineating the role of the VNO in human behavior.