Manipulating Neural Circuits with Optogenetic Equipment

神经科学的基本目标之一是了解不同类型的神经元如何在不同的大脑区域相互作用以指导行为。由于大脑中有许多类型的细胞及其广泛的相互联系，这个目标具有巨大的挑战性。即使特定类型的细胞可以被改变，结果往往是不确定的，因为操作通常是缓慢和不可逆的，允许大脑通过补偿来掩盖任何变化。此外，很少有技术能够在大脑使用的高速信息处理中改变神经元，这使得许多大脑-行为关系无法测试。然而，光遗传学方法克服了许多这些障碍，彻底改变了神经科学研究。这项技术的基础是发现，在藻类和细菌中天然存在的光敏蛋白质可以人工引入特定类型的神经元和特定的大脑区域。因此，这些蛋白质赋予这些神经元光敏感性，而不是邻近的神经元，使它们能够在大脑被光照时迅速打开和关闭。斯奈德博士将使用这种光遗传学设备来确定在成人大脑中出生的新神经元与在早期发育过程中出生的神经元的行为功能。Floresco博士将使用该设备来确定不同的大脑区域网络如何相互作用，以调节行为灵活性和决策。这两条研究路线都高度依赖于能够操纵神经元亚群的技术，这些神经元亚群嵌入在动物学习、回忆和决策的更大、更复杂的网络中。因此，本提案中描述的最先进的光遗传学设备将使我们对大脑中神经回路如何控制行为的理解取得重大进展。

One of the fundamental goals of neuroscience is to understand how different types of neurons, across different brain regions, interact to guide behaviour. This goal has been tremendously challenging due to the many types of cells in the brain and their vast interconnectedness. Even when specific types of cells can be altered, results are often inconclusive since manipulations are typically slow and irreversible, allowing the brain to mask any changes by compensation. Also, few techniques have been able to alter neurons at the high speeds of information processing used by the brain, leaving many brain-behaviour relationships untestable. Optogenetic methods, however, have revolutionized neuroscience research by overcoming many of these barriers. This technology is based on the discovery that light-sensitive proteins, found naturally in algae and bacteria, can be artificially introduced into specific types of neurons and in specific brain regions. These proteins therefore confer light-sensitivity to those neurons, but not neighboring neurons, enabling them to be rapidly turned on and off when the brain is illuminated with light. Dr. Snyder will use this optogenetic equipment to determine the behavioural function of new neurons that are born in the adult brain versus those that are born during early development. Dr. Floresco will use this equipment to identify how a diverse network of brain regions interacts to regulate behavioural flexibility and decision-making. Both of these lines of research are highly-dependent on techniques that can manipulate subpopulations of neurons that are embedded in larger, complex networks as animals learn, recall and make decisions. The state of the art optogenetics equipment described in this proposal will therefore lead to major advances in our understanding of how neural circuits in the brain govern behaviour.