PHYSIOLOGICAL DISSECTION OF THE SCN

描述（改编自申请人的摘要）：我们最近发现 由细胞标记的离散亚核是钙结合蛋白-D28 K（CaBP）阳性， 视交叉上核（SCN;银等，1996年）。 这些细胞接受 直接光输入，这是输入途径上细胞的预期特征， 起搏器，或直接在起搏器细胞内。 令我们惊讶的是， 该区域的离散损伤导致运动活性的丧失 节律性，即使这样的病变幸免于其他SCN室（显着 VIP和VP阳性细胞）。 相反，具有病变的动物， 使CaBP亚区免于持续的昼夜运动节律。 这些 结果表明，控制运动节律的起搏细胞 定位于CaBP阳性细胞区域。 挑战A 长期持有的假设-即SCN的任何部分都能够 维持昼夜节律。 这一概念很大程度上源于病变 研究，其中昼夜节律在部分 SCN的破坏，这导致大约25%的幸存者， 原子核 重申，以前的研究没有提供证据表明， 节奏性所必需的SCN区域，即使在个体中 动物，一个或另一个响应在损伤后丢失。 我们现建议 研究三个具体问题：1）CaBP亚核中的细胞是否 是运动以外的其他反应的昼夜节律所必需的 相关的节律（或者其他节律是否由不同的SCN控制 起搏器），2）CaBP中细胞的传入和传出连接 亚核，以及3）该亚核的细胞是否表达特性 （自由运行、夹带、相移）。 这 工作准备审查有关组织的基本问题， SCN：所有SCN细胞都是控制其他细胞节律的起搏器吗？ 大脑区域？ 有些细胞是振荡器，而振荡器又由SCN驱动 起搏器（或者，所有细胞都是起搏器）？ SCN的不同子集 细胞调节不同的节奏（达到不同的目标）？ 或者说， 调节所有昼夜节律的细胞核心

DESCRIPTION (Adapted from applicant's abstract): We recently discovered discrete subnuclei marked by cells are calbindin-D28K (CaBP)-positive within the suprachiasmatic nucleus (SCN; Silver et al., 1996). These cells receive direct photic input, a feature expected on cells on the input pathway to pacemakers, or directly within pacemaker cells. Much to our surprise, discrete lesions of this region resulted in loss of locomotor activity rhythmicity, even though such lesions spared other SCN compartments (marked by VIP- and VP-positive cells). Conversely, animals with lesions that spared the CaBP subregion sustained circadian locomotor rhythms. These results indicate that the pacemaker cells controlling locomotor rhythmicity are localized to the region of CaBP-positive cells. The results challenge a long held assumption - namely that any part of the SCN is capable of sustaining circadian rhythmicity. This notion derives largely from lesion studies, in which circadian rhythmicity is sustained following partial destruction of the SCN, which results in survival of about 25% of the nucleus. Restated, previous studies did not provide evidence for a critical area of the SCN necessary for rhythmicity, even though in individual animals, one or another response was lost following lesions. We now propose to examine three specific issues: 1) whether cells in the CaBP subnucleus are necessary for circadian rhythms in other responses other than locomotor- associated rhythms (or whether other rhythms are controlled by different SCN pacemakers), 2) the afferent and efferent connections of cells in the CaBP subnucleus, and 3) whether cells of this subnucleus express properties (free-running, entrainment, phase-shifting) expected of pacemakers. This work is poised to examine fundamental questions about the organization of the SCN: Are all SCN cells pacemakers controlling rhythmicity in other brain regions? Are some cells oscillators, which in turn are driven by SCN pacemakers (or, are all cells pacemakers)? Do different subsets of SCN cells regulate different rhythms (reach different targets)? Or, is there a core of cells that regulates all circadian rhythms?