Light direct effects on mood and cognitive functions

描述（由申请人提供）：在倒班和跨午线旅行中经历的异常光照条件，以及白天长度的季节性变化，会导致情绪和认知障碍。普遍的观点是，这些行为影响是由睡眠和昼夜节律的中断引起的。然而，我们最近表明，异常的光照时间表直接导致情绪和认知缺陷。哺乳动物视网膜包含三种主要的光感受器：视杆细胞、视锥细胞和内在光敏视网膜神经节细胞（ipRGCs），是所有依赖光的行为的光检测部位。iprgc表达光色素黑视素，并通过内在的黑视素光色素和光响应，也通过与传统rgc类似的杆/锥电路外部响应光。此外，ipRGCs投射到各种大脑区域，包括主昼夜节律起搏器以及与情绪和情绪调节有关的区域。我们已经确定iprgc是电路中的一个关键节点，它是破坏性光照计划对情绪和认知直接影响的基础。在这个提议中，我们的主要目标是确定视网膜回路和大脑目标，这些是异常光引起情绪和学习缺陷所必需的。具体来说，我们有几个视网膜小鼠突变体，这将使我们能够描绘出内在的基于黑视素的光导与外在的杆状/锥体输入对畸变光对情绪和认知的破坏性影响的相对贡献。此外，我们已经生成了多个小鼠系，在这些小鼠系中，我们特异性地切除或保留了iprgc的一个子集，该子集投射到主昼夜节律起搏器并驱动昼夜节律光干扰。为了确定足以承受畸变光负面影响的大脑区域，我们将使用光遗传学专门激活ipRGC终端，以模拟畸变光对单个大脑区域的影响。将突变小鼠系与这种光遗传学方法相结合，将使我们能够开始识别调节异常光照时间表如何导致情绪和学习缺陷的电路。这项研究结果将为设计更好的家庭、学校和工作环境的照明环境提供基础，以改善情绪和认知，从而提高生产力。另外，鉴定

DESCRIPTION (provided by applicant): Aberrant light conditions experienced during shift-work and transmeridian travel, as well as seasonal changes in day length, cause mood and cognitive deficits. The prevailing view is that these behavioral effects arise from disruptions in sleep and circadian rhythms. However, we have recently shown that aberrant light schedules directly lead to mood and cognitive deficits. The mammalian retina, which contains three major photoreceptors, rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs), is the site of light detection for all light-dependent behaviors. The ipRGCs express the photopigment melanopsin and respond to light both intrinsically via the melanopsin photopigment but also extrinsically through rod/cone circuitry, similar to conventional RGCs. Furthermore, ipRGCs project to a variety of brain regions that include the master circadian pacemaker as well as areas that have been implicated in mood and affect regulation. We have identified ipRGCs as a critical node in the circuit underling the direct effects of disruptive ligh schedule on mood and cognition. In this proposal, our major goals are to identify the retinal circuits and the brain targets that are necessary for aberrant light to cause mood and learning deficits. Specifically, we have several retinal mouse mutants that will allow us to delineate the relative contributions of the intrinsic melanopsin-based phototransduction versus the extrinsic rod/cone input to the disruptive effects of aberrant light on mood and cognition. In addition, we have generated multiple mouse lines where we have either specifically ablated or specifically retained a subset of ipRGCs that project to the master circadian pacemaker and drive circadian photoentrainment. To identify brain regions that are sufficient for the negative effects of aberran light, we will specifically activate ipRGC terminals using optogenetics, to mimic the effects of aberrant light on individual brain regions. The combination of mutant mouse lines with this optogenetic approach will allow us to begin to identify the circuits that mediate how aberrant light schedules lead to mood and learning deficits. The findings obtained from this proposal will provide a basis to design better lighting environments at homes, schools and work environment to improve mood and cognition leading to increased productivity. In addition, the identification of new brain circuits that impinge on mood regulation will provide new neuronal targets for the better use of light for therapeutic purposes.