Choi S, Wong L S, Yamat C, Dallman M F
Department of Physiology, University of California San Francisco, San Francisco, California 94143-0444, USA.
J Neurosci. 1998 May 15;18(10):3843-52. doi: 10.1523/JNEUROSCI.18-10-03843.1998.
Several endogenous oscillators determine circadian rhythms. One, light-entrained, is in the suprachiasmatic nuclei (SCN), the others, food-entrained, are in unknown sites. To determine how the hypothalamic ventromedial nuclei (VMN) and feeding affect rhythms, we compared nocturnally active rats fed either ad libitum or for 2 hr/d during light [restricted feeding (RF)] and either with or without colchicine-induced disruption of VMN. We measured rhythms in temperature, locomotor activity, feeding, drinking, corticosterone, and the numbers of cells expressing c-Fos in light/dark in hypothalamic nuclei, the suprachiasmatic nuclei, and two major SCN targets, the subparaventricular zone (sPVNz) and paraventricular thalamus (pvTHAL). c-Fos cells were always light > dark in SCN, whereas the VMN and sPVNz lacked light/dark differences except after RF and RF plus VMN disruption, respectively. Controls fed ad libitum had high-amplitude rhythms and, generally, c-Fos cells dark > light. In RF controls, a c-Fos pattern dark > light occurred in VMN; generally, c-Fos cell numbers increased elsewhere maintaining dark > light. By contrast, levels of corticosterone peaked before food. In rats fed ad libitum, VMN with colchicine markedly reduced rhythm amplitudes, not phase. c-Fos patterns were abolished except in pvTHAL and SCN. In RF, VMN disruption blocked corticosterone and light/dark c-Fos patterns in all nuclei but produced a pattern in the sPVNz like SCN. We conclude that VMN amplify rhythmic output from the SCN, and the RF-induced rhythm in VMN enhances c-Fos activity driven by the SCN. The VMN may contain a food-entrained oscillator, and the sPVNz may integrate output from several oscillators.
多个内源性振荡器决定昼夜节律。其中一个受光调节，位于视交叉上核（SCN），其他受食物调节，位置未知。为了确定下丘脑腹内侧核（VMN）和进食如何影响节律，我们比较了在光照期间随意进食或每天限时进食2小时[限时喂养（RF）]的夜间活动大鼠，以及有无秋水仙碱诱导的VMN破坏的大鼠。我们测量了体温、运动活动、进食、饮水、皮质酮的节律，以及下丘脑核、视交叉上核和两个主要的SCN靶点——室旁核下区（sPVNz）和室旁丘脑（pvTHAL）中表达c-Fos的细胞数量在明暗周期中的变化。c-Fos细胞在SCN中总是亮期>暗期，而VMN和sPVNz除了分别在RF和RF加VMN破坏后，没有明暗差异。随意进食的对照组有高振幅节律，一般来说，c-Fos细胞暗期>亮期。在RF对照组中，VMN出现了c-Fos模式暗期>亮期；一般来说，其他部位的c-Fos细胞数量增加，维持暗期>亮期。相比之下，皮质酮水平在进食前达到峰值。在随意进食的大鼠中，用秋水仙碱处理VMN显著降低了节律振幅，而不是相位。除了pvTHAL和SCN外，c-Fos模式被消除。在RF组中，VMN破坏阻断了所有核中的皮质酮和明暗c-Fos模式，但在sPVNz中产生了类似SCN的模式。我们得出结论，VMN放大了来自SCN的节律输出，RF诱导的VMN节律增强了由SCN驱动的c-Fos活性。VMN可能包含一个受食物调节的振荡器，而sPVNz可能整合了来自多个振荡器的输出。
