Leak R K, Moore R Y
Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
J Comp Neurol. 2001 May 7;433(3):312-34. doi: 10.1002/cne.1142.
The mammalian circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN), has two subdivisions. The core is located above the optic chiasm, receives primary and secondary visual afferents, and contains neurons producing vasoactive intestinal polypeptide and gastrin-releasing peptide. The shell largely surrounds the core, receives input from nonvisual sources and contains neurons producing arginine vasopressin and calretinin. In this study, we tested the hypothesis that SCN efferent projections are topographically organized with respect to the subdivision of origin. Injections of retrograde tracers were placed in major sites of efferent termination, described from prior studies that used anterograde tracers (Watts and Swanson, [1987] J. Comp. Neurol. 258:230-252; Watts et al. [1987] J. Comp. Neurol. 258:204-229). After retrograde tracer injections in the medial preoptic area, dorsomedial and paraventricular hypothalamic nuclei, bed nucleus of stria terminalis, paraventricular thalamic nucleus, zona incerta, and medial subparaventricular zone, retrogradely labeled SCN cells are clustered in the shell with few labeled neurons in the core. After injections centered in the lateral subparaventricular zone, peri-suprachiasmatic region, lateral septum, or ventral tuberal area, the majority of neuronal label is in the core with moderate to sparse neuronal label in the shell. Both subdivisions are labeled after injections in the paratenial thalamic nucleus. The same pattern of retrograde labeling is found with four tracers, cholera toxin-beta subunit, Fluoro-Gold, the Bartha strain of pseudorabies virus, and biotinylated dextran amine. These data extend our understanding of the significance of the division of the SCN into shell and core by demonstrating that the subdivisions differ in the pattern of projections. Together with prior observations that the subdivisions differ with respect to afferents, local connections, and neuroactive substances, the present study provides an anatomic basis for discrete control of circadian function by the SCN core and shell. In this novel view, the nature of the signal conveyed to areas receiving core or shell projections varies as a function of the subdivision from which innervation is derived.
哺乳动物的昼夜节律起搏器——下丘脑视交叉上核（SCN）有两个亚区。核心区位于视交叉上方，接受一级和二级视觉传入纤维，包含产生血管活性肠肽和胃泌素释放肽的神经元。外壳区主要围绕核心区，接受非视觉来源的输入，包含产生精氨酸加压素和钙视网膜蛋白的神经元。在本研究中，我们检验了一个假设，即SCN传出投射在拓扑结构上是根据起源亚区进行组织的。将逆行示踪剂注射到传出终末的主要部位，这些部位是根据先前使用顺行示踪剂的研究确定的（瓦茨和斯旺森，[1987]《比较神经学杂志》258:230 - 252；瓦茨等人[1987]《比较神经学杂志》258:204 - 229）。在内侧视前区、背内侧和室旁下丘脑核、终纹床核、室旁丘脑核、未定带和内侧室旁下区注射逆行示踪剂后，逆行标记的SCN细胞聚集在外壳区，核心区仅有少量标记神经元。在以外侧室旁下区、视交叉上核周围区域、外侧隔或腹侧结节区为中心进行注射后，大多数神经元标记位于核心区，外壳区有中度至稀疏的神经元标记。在丘脑旁核注射后，两个亚区均有标记。使用四种示踪剂——霍乱毒素β亚基、荧光金、伪狂犬病病毒的巴塔株和生物素化葡聚糖胺，发现了相同的逆行标记模式。这些数据通过证明亚区在投射模式上存在差异，扩展了我们对SCN分为外壳区和核心区意义的理解。结合先前关于亚区在传入纤维、局部连接和神经活性物质方面存在差异的观察结果，本研究为SCN核心区和外壳区对昼夜节律功能的离散控制提供了解剖学基础。按照这种新观点，传递到接受核心区或外壳区投射区域的信号性质会根据神经支配来源的亚区而有所不同。
