NEUROPEPTIDES IN THE CONTROL OF REPRODUCTIVE BEHAVIOR

描述(摘自申请者的摘要)：附属嗅觉 啮齿动物的系统(AOS)处理与以下有关的化学感觉信息 性别、生育条件和社会地位。进入的信号 AOS由犁鼻器(VNO)的感受器神经元检测，并被发送到 副嗅球(AOB)，随后到达下丘脑 脑垂体轴调节促性腺激素释放激素(GnRH)神经元。 在雌性小鼠身上，雄性小鼠的尿液和尿液衍生的化合物 证明可以改变GnRH介导的事件，如青春期加速和 发情周期。尿液和尿液化合物也会迅速升高c-fos AOB中mRNA的表达并直接改变VNO感觉的活动 神经元。本申请将利用这些化学传感器 刺激剂研究AOB中的信号处理。三个假设 构成具体目标：1)从空间上分离投影 AOB的VNO具有解剖学意义和功能意义； 小球周围细胞调制到达AOB的信号；3)化学感觉 信号在AOB的微电路中进行编码。神经解剖学 将使用轨迹追踪技术来绘制来自VNO的投影 AOB。AOB中的细胞激活模式将在 染毒后不同生理状态的雌性小鼠 具有不同生理状态的雄性或雌性。这些研究将界定 化学感觉信号传递中的解剖结构与功能关系 在VNO和AOB之间。电生理技术将是 用于研究膜的性质和神经递质的响应性 分离的AOB细胞、器官培养中的单层细胞和细胞 在切片准备过程中。这些研究将阐明这些调节作用。 球周细胞对二尖瓣细胞活动的影响。最后，与所有 电路完好无损，电生理技术将应用于 比较化学感官暴露和化学感官暴露的影响 VN神经刺激及评价药理阻滞剂的影响 VN末端给药对二尖瓣细胞活动的影响。 拟议中的实验将提供更好的理解 化学传感信号在到达GnRH之前被处理和编码 神经元，从而深入了解GnRH介导的神经内分泌控制 事件。这些结果可能有助于我们对这些机制的理解 人类女性潜在的周期性和生育能力，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.