Peripheral clocks in Drosophila

几十年来，果蝇和小鼠这两种主要动物模型系统的生物节律研究人员一直认为，行为节律完全由大脑中央时钟神经元决定。这些神经元起着起搏器的作用，可以产生24小时的运动周期，这对于让动物在一天中的最佳时间与环境互动非常重要。在果蝇中，起搏器细胞被称为sLNvs，在小鼠中，起搏器细胞被称为SCN。在苍蝇中，外周神经系统和非神经器官有独立的时钟，而在哺乳动物中，SCN通过许多信号因子同步外周的节律。最近，我们观察到，果蝇的触角或眼睛中的时钟位于大脑中枢之外，尽管中央时钟神经元在基因上是无节奏的，但它们仍能产生行为节奏。这意味着在这两种外周组织中存在能够调节节律性行为的起搏器细胞，所以这并不完全是slnv的问题。然而，天线中的时钟细胞需要大脑中枢网络保持完整，即使它是无时钟的，才能表达这些行为节律。这些结果会让飞行时钟研究人员感到震惊，因为它推翻了目前的教条。我们将仔细检查天线，并识别起行为起搏器作用的时钟细胞。我们知道这些细胞与温度，风和重力感知以及听觉有关，但它是这些的特定子集还是全部？触角也充满了嗅觉感受器，所以我们要问它们是否也能起起搏器细胞的作用。我们将以多种方式从基因上操纵这些细胞，例如，通过停止它们的时钟，过度刺激这些细胞，或加速或减慢它们的速度来观察节律性行为发生了什么变化。我们还将研究这些节律有多“正常”，它们对光和温度的反应是否和时钟一样正常，还是它们不正常？我们还将发现触角起搏器细胞是如何连接到节奏表达所必需的大脑中央回路的。我们将以类似的方式将我们的研究扩展到眼睛，最后我们将问非神经组织，苍蝇的肝脏称为脂肪体，是否也可以驱动行为节律。虽然这似乎不太可能，但鉴于我们已经取得的令人惊讶的结果，我们没有什么是理所当然的。

For several decades, biorhythm researchers in the two main animal model system, the fruitfly and the mouse have believed that behavioural rhythms are determined exclusively by central brain clock neurons. These neurons act as pacemakers and can generate the 24 hour locomotor cycles that are so important for allowing the animal to interact with its environment at the optimum time of day. In the fly, the pacemaker cells are called the sLNvs and in the mouse, the SCN. In the fly, the peripheral nervous system and non-neural organs have independent clocks, whereas in the mammal, the SCN synchronises the rhythms in the periphery via a number of signalling factors. Recently we have observed that clocks in the antennae or the eyes, which lie outside the central brain of the fruitfly, can nevertheless generate behavioural rhythms even though the central clock neurons are made genetically arrhythmic. This means there are pacemaker cells in these two peripheral tissues that can mediate rhythmic behaviour, so it is not all about the sLNvs. However, the clock cells in the antennae need the central brain network to be intact, even though it is clockless, in order for these behavioural rhythms to be expressed. These results will come as something of a shock to fly clock researchers as it overturns current dogma.We shall carefully examine the antennae and identify the clock cells that act as behavioural pacemakers. We know that these cells are involved in temperature, wind and gravity sensing as well as hearing, but is it particular subsets of these or is it all of them ? The antennae as also full of smell receptors, so we shall ask whether these too can act as pacemaker cells. We shall manipulate these cells genetically in a number of ways, for example by stopping their clocks, hyperexciting these cells, or speeding them up or slowing them down to see what happens to the rhythmic behaviour. We will also examine how 'normal' these rhythms are, do they respond to light and temperature in the usual ways that clocks do, or are they abnormal? We shall also find out how the antennal pacemaker cells might connect to the central brain circuit that is required for rhythms to be expressed. We will extend our studies to the eye in a similar way and finally we shall ask whether non-neural tissue, the fly's liver called the fat body, can also drive behavioural rhythms. While this might seem unlikely, given the surprising results that we have already obtained, we take nothing for granted.