NEURAL REGULATION OF CIRCADIAN RHYTHMS AND PHOTOPERIODIS

描述（改编自申请人的摘要）：松果体激素 褪黑激素（MEL）通过调节反馈来控制季节性繁殖， 性腺类固醇激素的行为作用。MEL还可以改变 内源性每日（昼夜）节律，或调节光的夹带效应。 昼夜节律和季节性繁殖都取决于 下丘脑视交叉上核（SCN）。高亲和力， gi偶联mel-1a膜受体明显介导生殖和at 至少是MEL的一些昼夜节律效应。这些实验将提供 我们更全面地了解mel-1a受体mRNA的分布， 以及在仓鼠中表达它的细胞的表型，并将探索 这些发现可能的生理意义。 第一个具体的目的是确定mel-1a受体mRNA是否在 在西伯利亚人SCN中的VIPergic和光响应mel-1a细胞中表达 仓鼠，其对MEL的反应取决于SCN的完整性。第二 具体目标将评估mel-1a、VIPergic和 SCN输出中的加压素能细胞可能有助于效应 MEL在西伯利亚仓鼠的光周期和昼夜娱乐中的作用。我们 将决定是否从投射逆向标记的细胞 SCN的区域含有mel-1amRNA。我们将确定光周期或 松果体切除对SCN终末AVP、VIP释放方式的影响 领域的第三个具体目标将评估 在实验中发现的共定位模式。激动剂或 将AVP或VIP的拮抗剂应用于SCN的投射野 传出神经和室内，以确定这些作用 光周期效应中的肽。如果我们发现mel-1a受体 在视网膜反应SCN细胞中表达，我们将确定是否 将生理浓度的MEL应用于SCN可以影响 昼夜节律相位或调制体内光的相移效应。这些 实验将阐明昼夜节律起搏器的基本功能， MEL的行动。这与人类健康和福祉特别相关，因为 数百万美国人一直在自我管理MEL，因为他们相信， 将产生广泛的有益影响。我们的结果会 应用于人类病理学，包括时差、睡眠障碍、季节性 抑郁症和不孕症。

DESCRIPTION (adapted from applicant's abstract): The pineal gland hormone melatonin (MEL) controls seasonal breeding by regulating feedback and behavioral actions of gonadal steroid hormones. MEL may also shift the phase of endogenous daily (circadian) rhythms, or modulate entraining effects of light. Both circadian rhythms and seasonal reproduction depend upon the suprachiasmatic nucleus of the hypothalamus (SCN). The high affinity, Gi-coupled mel-1a membrane receptor apparently mediates reproductive and at least some of the circadian effects of MEL. The proposed experiments will give us a more complete understanding of the distribution of mel-1a receptor mRNA and the phenotype of cells which express it in hamsters, and will explore the possible physiological implications of these findings. The first specific aim is to determine whether mel-1a receptor mRNA is expressed in VIPergic and light-responsive mel-1a cells in the SCN of Siberian hamsters, whose response to MEL depends upon integrity of the SCN. The second specific aim will evaluate the possible roles of mel-1a, VIPergic and vasopressinergic cells in outputs of the SCN which might contribute to effects of MEL in photoperiodism and circadian entertainment in Siberian hamsters. We will determine whether cells which are retrogradely labeled from projection fields of the SCN contain mel-1a mRNA. We will determine whether photoperiod or pinealectomy influence the pattern of release of AVP or VIP in SCN terminal fields. The third specific aim will evaluate the functional significance of the patterns of colocalization discovered in the experiments. Agonists or antagonists of AVP or VIP will be applied to projection fields of SCN efferents, and intraventricularly, in order to determine the role of these peptides in photoperiodic effects. If we find that mel-1a receptors are expressed in retinally responsive SCN cells, we will determine whether application of physiological concentrations of MEL to the SCN can influence circadian phase or modulate phase-shifting effects of light in vivo. These experiments will clarify the basic function of the circadian pacemaker and the actions of MEL. This is especially relevant to human health and welfare, since millions of Americans have been self-administering MEL in the belief that it will have a wide range of beneficial effects. Our results will have applications to human pathologies including jet lag, sleep disorders, seasonal depression, and infertility.