Spike After-Potentials of Oxytocin Cells in Lactation

描述(申请人提供)：我的研究兴趣主要集中在动物对不同生殖状态的生理适应。下丘脑视上核(SON)中的催产素(OT)神经元是研究这种适应的最佳模型之一，因为催产素在分娩和哺乳中的重要性已经得到了很好的证明。关于催产素神经元对哺乳期的神经元活动和形态反应的报道也很丰富。然而，OT神经元对哺乳的生理适应的潜在机制只有很少的讨论。众所周知，视上核中的OT神经元在分娩和哺乳期间因激素需求增加而经历神经元活动的显着变化。催产素神经元在每次排出乳汁之前表现出一个短的、高频的爆发(Poulain&Wakerley，1982)。突发性活动在所有OT神经元中是同步的(Belin等人，1984)，并导致OT大量释放到血流中，这是子宫收缩或乳腺肌上皮细胞收缩所必需的。这种脉动性被认为最大限度地发挥了OT的生物效应，并允许神经元从分泌疲劳中恢复(Bicknell，1988)。由于它们在控制激素分泌方面的重要性，涉及OT神经元的放电频率和模式的调节机制引起了人们的极大兴趣。神经元的电活动模式通常是内在离子机制和突触活动相互作用的结果。催产素神经元的固有膜特性，即峰后电位(超极化后电位(AHP)和去极化后电位(DAP))似乎发生了改变，有利于催产素神经元在分娩和哺乳过程中所必需的短时爆发活动。调节这些特性的离子电导至少部分参与了最终控制荷尔蒙释放的激发速率和模式的调节。因此，本研究旨在阐明催产素神经元在哺乳过程中生理特性发生变化的机制。该应用的具体目的是确定1)在哺乳过程中，峰后电位(AHPs和DAP)的哪个特定成分发生变化；2)该反应成分是否对性腺类固醇的变化有反应。

DESCRIPTION (provided by applicant): My research interest has been focused on the physiological adaptation of animals to their different reproductive states. The oxytocin (OT) neuron in the supraoptic nucleus (SON) of the hypothalamus is one of the best models to study such adaptation, because the importance of OT during parturition and lactation are well documented. The reports of neuronal activity and morphological responses of OT neurons to lactation are abundant as well. However, the mechanisms underlying the physiological adaptation of OT neurons to lactation are only sparsely discussed. OT neurons in the supraoptic nucleus are known to undergo a remarkable change in neuronal activity in response to the increased hormonal demand that occurs during parturition and lactation. OT neurons display a short, high frequency burst proceeding each milk ejection (Poulain & Wakerley, 1982). The bursting activity is synchronized among all OT neurons (Belin et al., 1984) and results in a bolus release of OT into the blood stream, necessary for uterine contraction or contraction of myoepithelial cells in the mammary glands. This pulsatility is believed to maximize the biological effects of OT and allows the neurons to recover from secretory fatigue (Bicknell, 1988). Because of their significance in controlling hormone secretion, mechanisms involve in the regulation of firing rate and pattern in OT neurons are the subject of great interest. The pattern of electrical activity of neurons generally results from the interaction of intrinsic ionic mechanisms and synaptic activity. The intrinsic membrane properties of OT neuron, the spike after-potentials (after hyperpolarizing potentials (AHP) and depolarization after-potential (DAP)), appear to change in favor of the short bursting activity of OT neuron necessary during parturition and lactation. The ionic conductances mediating these properties are, at least partly, involving in the regulation of the firing rate and pattern that ultimately control the release of hormone. Therefore, this application is to elucidate the mechanisms responsible for the changes in physiological properties of OT neurons in response to lactation. The specific aims of the application are to determine 1) what specific component of spike after-potentials (AHPs and DAP) is altered during lactation; 2) whether the responsive component is responsive to changes in the gonadal steroids.