NEUROPEPTIDES IN THE CONTROL OF REPRODUCTIVE BEHAVIOR

描述（改编自申请人的摘要）：附件嗅觉 啮齿动物的化学感觉系统（AOS）处理有关化学感觉的信息 性别、生育状况和社会地位。 信号进入 AOS由犁鼻器（VNO）的受体神经元检测，发送到 副嗅球（AOB），随后到下丘脑 垂体轴调节促性腺激素释放激素（GnRH）神经元。 在雌性小鼠中，雄性尿液和尿液衍生化合物已被 证明可以改变GnRH介导的事件，如青春期加速， 发情周期 尿液和尿中化合物也迅速升高c-fos AOB中mRNA的表达并直接改变VNO感觉神经元的活性 神经元 本申请将利用这些化学传感器。 研究AOB中信号处理的刺激因素。 三个假设 构成具体目标：1）投影的空间分离， AOB的VNO在解剖学和功能上具有重要意义; 2） 肾小球周围细胞调节到达AOB的信号; 3）化学感受 信号被编码在AOB的微电路中。 神经解剖 将使用轨迹跟踪技术来绘制来自VNO的投影 的AOB。 AOB中的细胞活化模式将在 不同生理状态的雌性小鼠在暴露于来自 不同生理状态的男性或女性。 这些研究将定义 化学感受信号解剖结构与功能关系 在VNO和AOB之间。 电生理技术将是 应用于研究膜特性和神经递质反应性 分离的AOB细胞、器官型培养物中的单层细胞和 在切片制备中。 这些研究将阐明调节作用 对二尖瓣细胞活性的影响。 最后，与所有 电路完整，电生理技术将应用于 整个动物，以比较化学感觉暴露与 VN神经刺激并评估药理学阻滞剂的影响 在VN末端施用对二尖瓣细胞的活性的影响。 拟议的实验将提供一个更好的理解如何 化学感觉信号在到达GnRH之前被处理和编码 神经元，从而提供深入了解GnRH介导的神经内分泌控制 事件 这些结果可能有助于我们理解这些机制。 潜在的周期性和生育能力在人类女性，并可能指导未来 努力描绘VNO在人类行为中的作用。

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.