MULTI-OSCILLATOR SIGNALS IN CIRCADIAN ENERGY REGULATION

说明(改编自应用程序) 下丘脑腹内侧核(VMN)是昼夜节律的基础 调节能量平衡。VMN的病变会产生高胰岛素血症和 摄食的昼夜节律的幅度显著降低， 下丘脑-垂体-肾上腺功能、体温和运动 活动。这些影响的组合最终会导致肥胖。 此外，这些昼夜节律可以从由 视交叉上核(SCN；主生物钟)对食物线索的反应 由VMN提供。节律对食物摄入量的夹带发生在食物摄入量 仅限于光照阶段的很短时间内(大鼠是夜间活动的 并在黑暗时期进食)，以及当VMN中的活动完好无损时。损伤 可以防止这种节律的改变。然而，这些机制和/或 VMN对体重和昼夜节律产生这些影响的回路 节律大多是未知的。这项建议提出的假设是： 1)VMN放大调节神经元c-Fos节律的SCN振荡输出 在已知的控制能量平衡的大脑区域；以及，2)不同 限制摄食过程中VMN中表达的基因参与调控 VMN对昼夜能量平衡的影响。SHAM与SCN的比较 损毁的大鼠将被用来确定大脑中的昼夜c-Fos节律 都被废除了。VMN中差异表达基因的鉴定 在限制喂养和自由喂养之间制作大鼠，因为VMN是 对于通过限制摄食来改变昼夜节律是必要的。 抑制消减杂交将用于分离和鉴定 VMN中差异表达的基因，这可能导致识别 用于调节昼夜节律和能量平衡的信号。中的像差 昼夜节律调节能量平衡可能与病理有关，例如 肥胖、饮食和情感障碍，如抑郁症。这些实验 和技术有助于实现长期研究目标，以调查 神经系统整合了昼夜节律，这些节律由几个 振荡器，这样的系统的优势将提供，新陈代谢 破坏这样一个系统的后果。调查这些问题，从 生理、内分泌和分子方面的观点将有助于 机制与功能相结合。三年的博士后培训 加州大学旧金山分校已经提供了强大的技术和研究技能， 对Sujean Choi博士的研究生涯发展起到了积极的作用。这个 继续在加州大学旧金山分校和玛丽·F·达尔曼博士的实验室进行研究 将提供一种多学科的研究方法，并提供重要的 在学术环境中从事研究事业的优势。

DESCRIPTION (adapted from the application) The hypothalamic ventromedial nuclei (VMN) are fundamental to the circadian regulation of energy balance. Lesions of the VMN produce hyperinsulinema and a marked reduction in the amplitudes of circadian rhythms of feeding, hypothalamic-pituitary-adrenal function, body temperature, and locomotor activity. The combination of these effects ultimately leads to obesity. Moreover, these circadian rhythms can be shifted from light cues provided by the suprachiasmatic nuclei (SCN; master biological clock) to food cues provided by the VMN. Entrainment of rhythms to food intake occurs when food intake is restricted to a very short period during the light phase (rats are nocturnal and eat during the dark period) and when activity in the VMN is intact. Lesions of the VMN prevent this shift in rhythms. However, the mechanisms and/or circuitry by which the VMN exert these effects on body weight and circadian rhythms are mostly unknown. The hypotheses presented in this proposal are that: 1) the VMN amplify SCN oscillatory outputs that regulate neuronal c-Fos rhythms in brain regions known to control energy balance; and, 2) differentially expressed genes in the VMN during restricted feeding participate in regulation of circadian energy balance by the VMN. Comparisons between sham and SCN lesioned rats will be made to determine if diurnal c-Fos rhythms in the brain are abolished. Identification of differentially expressed genes in the VMN between restrict fed and ad libitum fed rats will be made since VMN are necessary for the entrainment of circadian rhythms by restricted feeding. Suppression subtractive hybridization will be used to isolate and identify differentially expressed genes in the VMN, which may lead to identification of signals used to regulate circadian rhythms and energy balance. Aberrations in circadian regulation of energy balance may be linked to pathologies such as obesity, eating , and affective disorders such as depression. These experiments and techniques contribute to long-term research goals to investigate how the nervous system integrates circadian rhythms that are regulated by several oscillators, the advantages of such a system would provide, and the metabolic consequences of disruption of such a system. Investigating these questions from physiological, endocrinological, and molecular perspectives will help to integrate mechanisms with function. Three years of post-doctoral training at UCSF have already provided strong technical and research skills that have positively shaped the development of a research career for Dr SuJean Choi. The continuation of research at UCSF and in the laboratory of Dr. Mary F. Dallman would provide a multidisciplined approached to research and offer significant advantages for pursuing a research career in an academic setting.