Retinal Inputs to the Mammalian Circadian Pacemaker

描述（由候选人提供）：所有生物在其生理过程中都表现出被称为昼夜节律的每日周期性变化，在哺乳动物中，这种节律是由视交叉上核（SCN）内部驱动的。这些内部节律每天被太阳周期重置（“夹带”），因此它们与外部的光/暗周期相一致。内部和外部节律的不同步会导致“时差”症状，这可能会对健康造成严重后果。除了经典的光感受器，即视杆细胞和视锥细胞外，最近发现的内在光敏视网膜神经节细胞（ipRGCs）也参与了夹带。虽然杆状/锥状细胞和ipRGCs在生理上是不同的，但它们在夹带中的不同作用却知之甚少。此外，杆/锥系统与iprgc之间的相互作用尚未被探索。在这个项目中，这两个问题将在视网膜和SCN水平上进行研究，使用膜片钳和细胞外记录技术结合药理学操作。这些实验可能使我们更好地了解哺乳动物的昼夜节律起搏器是如何被调节的，从而可能带来更好的治疗方法和工作场所政策，以对抗/预防时差问题。

DESCRIPTION (provided by candidate): All organisms display daily cyclical changes known as circadian rhythms in their physiological processes, and in mammals such rhythms are driven internally by the suprachiasmatic nucleus (SCN). These internal rhythms are reset ("entrained") daily by the solar cycle so that they are in phase with the external light/dark cycle. Desynchronization between the internal and external rhythms results in "jet lag" symptoms which can have serious health consequences. Besides the classical photoreceptors, that is, rods and cones, the recently identified intrinsically photosensitive retinal ganglion cells (ipRGCs) are also involved in entrainment. While the rods/cones and the ipRGCs are known to be physiologically distinct, their differential roles in entrainment are poorly understood. In addition, interactions between the rod/cone system and the ipRGCs have not been explored. In this project, both issues will be studied at the retinal and the SCN levels, using patch-clamp and extracellular recording techniques combined with pharmacological manipulations. These experiments may enable a better understanding of how the mammalian circadian pacemaker is regulated, which in turn may lead to better therapies and workplace policies combating/preventing jet lag problems.