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，跨越不同的大脑区域，如何相互作用来指导行为。这一目标具有极大的挑战性，因为大脑中有多种类型的细胞，它们之间存在着巨大的相互联系。即使特定类型的细胞可以改变，结果通常也是不确定的，因为操作通常是缓慢的和不可逆的，允许大脑通过补偿来掩盖任何变化。此外，很少有技术能够以大脑使用的高速信息处理来改变神经元，这使得许多大脑与行为的关系无法测试。然而，光遗传学方法克服了许多这些障碍，使神经科学研究发生了革命性的变化。这项技术是基于一项发现，即天然存在于藻类和细菌中的光敏蛋白可以被人工引入特定类型的神经元和特定的大脑区域。因此，这些蛋白质将光敏感度赋予这些神经元，而不是邻近的神经元，使它们在大脑受到光线照射时能够迅速打开和关闭。斯奈德博士将使用这种光遗传学设备来确定成年大脑中新生的神经元与早期发育中出生的神经元的行为功能。弗洛雷斯科博士将使用这种设备来识别大脑区域的不同网络如何相互作用，以调节行为的灵活性和决策。这两个研究方向都高度依赖于一些技术，这些技术可以在动物学习、回忆和做出决定的过程中操纵嵌入在更大、更复杂网络中的神经元亚群。因此，这项提案中描述的最先进的光遗传学设备将使我们在理解大脑中的神经电路如何控制行为方面取得重大进展。

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.