Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA.
Eur J Neurosci. 2011 Aug;34(3):478-88. doi: 10.1111/j.1460-9568.2011.07762.x. Epub 2011 Jul 21.
Although much is known about the regulation of the circadian rest-activity cycle by the hypothalamic suprachiasmatic nucleus in nocturnal rodents, little is known about the neural substrates that regulate the temporal organization of nocturnal activity within the active phase. In this report, data are presented in Syrian hamsters to implicate the habenula - believed to be involved in motivation, reward and motor control--as a candidate site for such a role. First, by examining hamsters during the day and night and by introducing a 'novel' running wheel in order to induce daytime motor activity, we showed that immunoreactive c-Fos expression in the lateral and medial habenula is related to motor activity/arousal. Second, by transecting the habenula's major efferent pathway (fasciculus retroflexus), we showed that the interruption of habenula neural output alters the daily amount of motor activity, lengthens the period of the circadian rest-activity rhythm and disrupts the species-typical pattern of nocturnal motor activity, measured as either wheel-running behavior or general locomotor activity. Instead of the usual pattern of night-time locomotion, characterized by a prolonged bout of elevated activity in the early night followed by shorter sporadic bouts or the cessation of activity altogether, lesioned animals exhibited a more homogeneous, undifferentiated temporal profile extending across the night. These data suggest a previously unrecognized function of the habenula whereby it regulates the temporal pattern of activity occurring within a circadian rest-activity window set by the suprachiasmatic nucleus.
尽管人们对下丘脑视交叉上核（suprachiasmatic nucleus）调节夜间啮齿动物昼夜节律活动-休息周期的机制了解较多，但对于调节活跃期内夜间活动时间组织的神经基础知之甚少。本研究报告以叙利亚仓鼠为模型，提示缰核（believed to be involved in motivation, reward and motor control）可能在其中发挥作用。首先，通过日间和夜间检测仓鼠，并引入“新颖”的跑轮以诱导日间运动活动，我们发现缰核外侧和内侧的 c-Fos 免疫反应性表达与运动活动/觉醒有关。其次，通过横断缰核的主要传出通路（fasciculus retroflexus），我们发现缰核神经输出的中断会改变日间运动量，延长昼夜节律活动的周期，并破坏夜间运动活动的典型模式，表现为跑轮行为或一般运动活动。与夜间运动的典型模式（即夜间早期长时间的活动高峰，随后是较短的零星发作或完全停止活动）不同，损伤动物表现出更均匀、无差别的时间分布，跨越整个夜间。这些数据表明缰核具有先前未被认识到的功能，它调节由视交叉上核设定的昼夜节律活动-休息窗口内的活动时间模式。
