Optogenetics in Drosophila Neuroscience.
Optogenetics in Drosophila Neuroscience.
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DOI：
10.1007/978-1-4939-3512-3_11
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发表时间：
2016
影响因子：
--
通讯作者：
T. Riemensperger;R. Kittel;A. Fiala
中科院分区：
文献类型：
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作者：
T. Riemensperger;R. Kittel;A. Fiala
光遗传学技术使人们能够用光敏蛋白质靶向特定的神经元，例如，离子通道、离子泵或酶，并通过照明来操纵它们的生理状态。这种对复杂神经元回路的选定元件的人工干扰可以帮助确定神经元活动与对控制动物行为的神经元回路的功能的影响之间的因果关系。光遗传学的优势可以在遗传上易于处理的动物中得到最好的利用，一方面，这些动物的神经系统在细胞数量方面足够小，并且在一定程度上具有刻板的组织，使得可以重复地靶向不同和可识别的神经元。另一方面，神经元回路和行为库应该足够复杂，以使人们能够解决有趣的问题。果蝇（Drosophila melanogaster）是这方面的一个良好的模式生物。然而，在成年果蝇中，通过光诱导的离子电流将光遗传学工具应用于去兴奋或过度兴奋神经元一直很困难。直到最近，已经引入了几种ChR-2的变体，它们提供了足够的光敏性、表达和稳定性，以有效地在成年果蝇中使中枢脑神经元去极化。在这里，我们专注于目前提供最高光刺激效率的版本，ChR 2-XXL。我们通过将其应用于广泛使用的厌恶性嗅觉学习范式来验证这种光遗传学工具的使用。一群多巴胺释放神经元的光遗传激活模拟了惩罚性电击的强化特性，通常用作无条件刺激。在与气味刺激的时间重合中，这种人工诱导的神经元活动引起气味信号的学习，从而产生光诱导的记忆。
Optogenetic techniques enable one to target specific neurons with light-sensitive proteins, e.g., ion channels, ion pumps, or enzymes, and to manipulate their physiological state through illumination. Such artificial interference with selected elements of complex neuronal circuits can help to determine causal relationships between neuronal activity and the effect on the functioning of neuronal circuits controlling animal behavior. The advantages of optogenetics can best be exploited in genetically tractable animals whose nervous systems are, on the one hand, small enough in terms of cell numbers and to a certain degree stereotypically organized, such that distinct and identifiable neurons can be targeted reproducibly. On the other hand, the neuronal circuitry and the behavioral repertoire should be complex enough to enable one to address interesting questions. The fruit flyDrosophila melanogasteris a favorable model organism in this regard. However, the application of optogenetic tools to depolarize or hyperpolarize neurons through light-induced ionic currents has been difficult in adult flies. Only recently, several variants of Channelrhodopsin-2 (ChR2) have been introduced that provide sufficient light sensitivity, expression, and stability to depolarize central brain neurons efficiently in adultDrosophila. Here, we focus on the version currently providing highest photostimulation efficiency, ChR2-XXL. We exemplify the use of this optogenetic tool by applying it to a widely used aversive olfactory learning paradigm. Optogenetic activation of a population of dopamine-releasing neurons mimics the reinforcing properties of a punitive electric shock typically used as an unconditioned stimulus. In temporal coincidence with an odor stimulus this artificially induced neuronal activity causes learning of the odor signal, thereby creating a light-induced memory.