TIRANT: A novel transsynaptic labeling approach to map neuronal circuits

大脑不仅仅是其各部分的总和。要真正理解大脑最复杂的特性，需要对它所包含的神经元类型进行普查，并绘制出这些部分如何相互连接形成功能电路的地图。据估计，哺乳动物的大脑由数百种神经元组成，每种神经元都嵌入复杂的回路中。我们这一代人面临的挑战包括绘制这些神经元群体之间的连接。目前映射电路的方法具有限制，这阻止了它们的广泛采用和在高通量实验中的使用。我们提出了一种新的transsynaptic标签的方法，这将使互联的神经元群体的映射通过结合的遗传编码的配体的合成受体跨越突触间隙。这种方法将允许遗传靶向神经元回路的突触前和突触后成分，从而促进回路功能的研究。我们将证明我们的方法的有用性映射的两个不同的神经元群体的跨突触连接投射到核的神经元，一个结构的关键奖励处理。这一提议的影响超出了对奖赏回路的理解，并提供了一个新的工具集来完成绘制大脑神经元回路的艰巨任务。

The brain is more than the sum of its parts. Truly understanding the brain's most intricate properties requires both a census of the types of neurons it contains and a map of how these parts are interconnected to form functional circuits. It is estimated that several hundred types of neurons compose the mammalian brain, each embedded within complex circuits. The challenge of our generation consists of mapping the connection between these neuronal populations. Current approaches to map circuits have limitations that prevent their widespread adoption and their use in high-throughput experiments. We propose a novel transsynaptic labelling approach that will enable the mapping of interconnected neuronal populations through the binding of a genetically-encoded ligand to a synthetic receptor across the synaptic cleft. This method will allow genetic targeting of the pre- and post-synaptic components of neuronal circuits, and thus facilitates the investigation of circuit function. We will demonstrate the usefulness of our approach by mapping the transsynaptic connections of two distinct neuronal populations projecting to the nucleus accumbens, a structure critical to reward processing. The impact of this proposal extends beyond the understanding of the reward circuitry and provide a new toolset to accomplish the daunting task of mapping the brain's neuronal circuits.