Circadian photoreception in Drosophila melanogaster

描述（由申请人提供）：生物钟是关键的计时机制。它们确保大多数身体功能——从基本的细胞生物化学到复杂的行为，如睡眠-觉醒周期——都能适当地适应一天中的时间。生物钟是自我维持的：即使在恒定的环境条件下，它们也会持续存在。然而，生物钟需要每天重新设置，以与环境保持适当的阶段性，因为它们的周期长度并不完全是24小时。光是生物钟的关键输入。因此，我们的目标是了解昼夜节律光接受的神经和分子机制，以果蝇为模型生物。我们的初步数据表明，两组昼夜节律神经元，M-和e -振荡器，形成了一个神经网络，使果蝇能够根据光输入重置其昼夜节律行为。因此，我们的第一个目标将阐明M-和e -振荡器如何相互通信，以在暴露于光后重置昼夜节律行为。我们将定义M-和e -振荡器在昼夜节律光反应中的神经传递各自的作用。我们还将确定M-和e -振荡器在响应光输入时重置昼夜节律行为所需的神经递质和受体。我们的第二个目标是在分子水平上研究光输入如何到达M-和e -振荡器中的昼夜节律起搏器。我们将确定细胞自主昼夜感光机制的作用，并阐明起搏器在昼夜感光过程中如何响应神经输入。因此，拟议的工作将是对果蝇昼夜节律光接受的全面研究，从基本的细胞自主机制同步昼夜节律神经元中的分子起搏器，到控制昼夜节律光反应的神经元之间的相互作用。由于果蝇的昼夜节律神经网络相对简单，我们将能够以非常精确的水平理解昼夜节律的光接受。在哺乳动物中，昼夜行为节律的同步依赖于分子输入通路，这些分子输入通路重置了光敏感昼夜节律神经元中的昼夜节律钟，然后将光信息传递给视交叉上核（哺乳动物大脑起搏器）的其余部分。因此，我们预计我们的工作将揭示动物昼夜节律同步的一般原理。这些原则最终可能被证明对理解和治疗与昼夜节律与昼夜周期失调相关的疾病很重要，这在许多睡眠和情绪障碍中都可以观察到。

DESCRIPTION (provided by applicant): Circadian clocks are critical time-keeping mechanisms. They ensure that most bodily functions - from basic cellular biochemistry to complex behaviors such as the sleep-wake cycle - are properly adapted to the time of day. Circadian clocks are self-sustained: they persist even under constant environmental conditions. Nevertheless, circadian clocks need to be reset every day to remain properly phased with the environment, because their period length is not exactly 24hr. Light is a critical input for circadin clocks. Our goal is therefore to understand the neural and molecular mechanisms underlying circadian photoreception, using as a model organism Drosophila melanogaster. Our preliminary data demonstrate that two small groups of circadian neurons, the M- and E-oscillators, form a neural network that allows Drosophila to reset their circadian behavior in response to light inputs. Our first aim will thus elucidate how the M- and E-oscillators communicate with each other to reset circadian behavior after exposure to light. We will define the respective role of neurotransmission in M- and E-oscillators for circadian photoresponses. We will also identify the neurotransmitters and the receptors required for M- and E-oscillators to reset circadian behavior in response to light inputs. Our second aim will study at the molecular level how light input reaches circadian pacemakers in the M- and E-oscillators. We will determine the role of cell-autonomous circadian photoreceptive mechanisms, as well as elucidate how pacemakers respond to neural input during circadian photoresponses. The proposed work will thus be a comprehensive study of circadian photoreception in Drosophila, from basic cell-autonomous mechanisms synchronizing the molecular pacemakers in circadian neurons, to interactions between neurons that control circadian photoresponses. Because of the relative simplicity of the Drosophila circadian neural network, we will be able to understand circadian photoreception with a remarkable level of precision. In mammals also, synchronization of circadian behavioral rhythms is dependent on molecular input pathways that reset circadian clocks in light- sensitive circadian neurons, which then communicate light information to the rest of the Suprachiasmatic Nucleus, the mammalian brain pacemaker. We thus anticipate that our work will uncover general principles underlying synchronization of circadian rhythms in animals. These principles could ultimately prove important to understand and treat diseases associated with the misalignment of circadian rhythms with the day/night cycle, which is observed in many sleep and mood disorders.