TIRANT: A novel transsynaptic labeling approach to map neuronal circuits

大脑不仅仅是各个部分的总和。真正了解大脑最复杂的特性需要对大脑中包含的神经元类型进行普查，并绘制出这些部分是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电路中。我们这一代人的挑战包括绘制这些神经元群体之间的联系。目前绘制电路图的方法具有局限性，阻碍了它们在高通量实验中的广泛采用和使用。我们提出了一种新的跨突触标记方法，该方法将通过将遗传编码的配体与跨越突触间隙的合成受体结合来映射相互连接的神经元群体。这种方法将允许对神经元回路突触前和突触后成分进行基因靶向，从而促进对回路功能的研究。我们将通过映射投射到伏隔核的两个不同神经元群体的跨突触连接来证明我们方法的有效性，伏隔核是奖励处理的关键结构。这一提议的影响超出了对奖励电路的理解，并提供了一个新的工具集来完成绘制大脑神经元电路的艰巨任务。

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.