PHYSIOLOGICAL DISSECTION OF THE SCN

描述(改编自申请者摘要)：我们最近发现 细胞标记的离散亚核内Calbindin-D28K(CABP)阳性 视交叉上核(SCN；Silver等人，1996)。这些细胞接收 直接光输入，这是输入路径上的细胞所期望的一个特征 起搏器，或直接在起搏器细胞内。令我们惊讶的是， 这一区域的离散病变导致活动能力丧失 节律性，即使这样的损害没有其他SCN间隔(标记的 VIP和VP阳性细胞)。相反，有损伤的动物 CABP次区域没有出现昼夜运动节律。这些 结果表明，控制运动节律性的起搏细胞 定位于CABP阳性细胞区域。这一结果挑战了 长期以来的假设--即SCN的任何部分都有能力 维持昼夜节律的。这一概念在很大程度上源于病变 在这些研究中，昼夜节律性在部分节律之后保持 破坏SCN，导致大约25%的 原子核。重申一下，之前的研究并没有提供证据证明 节律性所必需的SCN区域，即使在个体中 动物，一种或另一种反应在损伤后消失。我们现在提议 要检查三个具体问题：1)CABP亚核中的细胞 对于运动以外的其他反应中的昼夜节律是必要的- 相关节律(或其他节律是否由不同的SCN控制 起搏器)；2)CABP内细胞的传入和传出联系 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)对起搏器的期望。这 工作准备检查有关组织的基本问题 SCN：是不是所有SCN细胞的起搏器都控制着其他 大脑区域？是一些细胞振荡器，而细胞振荡器又由SCN驱动 起搏器(或者，所有的细胞都是起搏器)？执行SCN的不同子集 细胞调节不同的节律(达到不同的目标)？或者，有没有 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?