Circuit projection from suprachiasmatic nucleus to ventral tegmental area: a novel circadian output pathway
Circuit projection from suprachiasmatic nucleus to ventral tegmental area: a novel circadian output pathway
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DOI：
10.1111/j.1460-9568.2008.06606.x
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发表时间：
2009-02-01
影响因子：
3.4
通讯作者：
Aston-Jones, Gary
中科院分区：
文献类型：
--
作者：
Luo, Alice H.;Aston-Jones, Gary
视交叉上核（SCN）是一个同步许多重要过程的昼夜节律起搏器。尽管大量的研究集中在SCN的输入通路和中央时钟本身，但对SCN输出信号通路的了解相对较少。腹侧被盖区（VTA）因其对动机学习的影响而被广泛研究，最近又因其在觉醒和睡眠-觉醒调节中的潜在作用而被研究。在这里，我们提供了SCN通过内侧视前核（MPON）间接投射到VTA的数据。在大鼠VTA中微量注射逆行、跨突触示踪剂伪狂犬病毒（PRV），在指示间接电路投射的时间点一致地标记SCN神经元。为了确定SCN和VTA之间的中间传递核，在VTA注射PRV前1周对假定的传递核进行损伤。单侧MPON病变使SCN中的PRV标记在同侧半球减少81.6%，在对侧半球减少75.8%。双侧尾背侧隔（另一个假定的中继核和背侧注射控制点）的病变并没有显著降低SCN中的PRV标记。在氟烷麻醉下的单细胞外记录显示，在活跃的昼夜节律阶段，有一种新的VTA神经元群选择性地放电。这些结果表明，SCN通过MPON为VTA提供了一个间接的电路通路，并且VTA神经元的冲动活动表现出昼夜节律。这条通路可能在包括觉醒和动机在内的许多行为过程的昼夜节律调节中起作用。
The suprachiasmatic nucleus (SCN) is a circadian pacemaker that synchronizes a number of vital processes. Although a great deal of research has focused on input pathways to SCN and on the central clock itself, relatively little is known about SCN output signaling pathways. The ventral tegmental area (VTA) has been extensively studied for its influence in motivated learning and, recently, for a potential role in arousal and sleep-wake regulation. Here we present data that SCN indirectly projects to VTA via the medial preoptic nucleus (MPON). Microinjection of the retrograde, transynaptic tracer pseudorabies virus (PRV) in rat VTA consistently labeled SCN neurons at time points indicative of an indirect circuit projection. To specify intermediate relay nuclei between SCN and VTA, putative relays were lesioned 1 week prior to PRV injections in VTA. Unilateral lesions of MPON reduced PRV labeling in SCN by 81.6% in the ipsilateral hemisphere and 75.8% in the contralateral hemisphere. Bilateral lesions of the caudal-dorsal lateral septum, another putative relay nucleus and dorsal injection control, did not significantly reduce PRV labeling in the SCN. Single-unit extracellular recordings under halothane anesthesia revealed a novel population of VTA neurons that selectively fired during the active circadian phase. These results show that SCN provides an indirect circuit pathway to VTA via MPON, and that VTA neurons exhibit a circadian rhythm in their impulse activity. This pathway may function in the circadian regulation of numerous behavioral processes including arousal and motivation.