Connect-seq to superimpose molecular on anatomical neural circuit maps
Connect-seq to superimpose molecular on anatomical neural circuit maps
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DOI：
10.1073/pnas.1912176117
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发表时间：
2020-02-25
影响因子：
11.1
通讯作者：
Buck, Linda B.
中科院分区：
文献类型：
--
作者：
Hanchate, Naresh K.;Lee, Eun Jeong;Buck, Linda B.
小鼠的大脑包含大约7500万个神经元，这些神经元相互连接在一个巨大的神经回路中。大多数电路的单个神经元组件的身份和功能是未知的。在这里，我们描述了一种名为“Connect-seq”的方法，它结合了逆行病毒跟踪和单细胞转录，以揭示特定电路中上游神经元的分子身份及其用于通信的信号分子。CONNECT-SEQ可以生成一个分子图，该图可以叠加在神经解剖图上，以允许对电路的神经元组件如何控制其功能进行分子和遗传询问。将这种方法应用于控制对恐惧和压力的生理反应的下丘脑神经元，揭示了上游神经元的亚群，这些亚群表达不同的信号分子星座，并可以根据它们的解剖位置来区分。
The mouse brain contains about 75 million neurons interconnected in a vast array of neural circuits. The identities and functions of individual neuronal components of most circuits are undefined. Here we describe a method, termed "Connect-seq," which combines retrograde viral tracing and single-cell transcriptomics to uncover the molecular identities of upstream neurons in a specific circuit and the signaling molecules they use to communicate. Connect-seq can generate a molecular map that can be superimposed on a neuroanatomical map to permit molecular and genetic interrogation of how the neuronal components of a circuit control its function. Application of this method to hypothalamic neurons controlling physiological responses to fear and stress reveals subsets of upstream neurons that express diverse constellations of signaling molecules and can be distinguished by their anatomical locations.