Brain-wide circuit-specific targeting of astrocytes.
Brain-wide circuit-specific targeting of astrocytes.
复制标题
DOI：
10.1016/j.crmeth.2023.100653
复制
发表时间：
2023-12-18
期刊：
影响因子：
--
通讯作者：
Xu, Wei
中科院分区：
文献类型：
--
作者：
Thompson, Alyssa;Arano, Rachel;Saleem, Uzair;Preciado, Rebecca;Munoz, Lizbeth;Nelson, Ian;Ramos, Katarina;Kim, Yerim;Li, Ying;Xu, Wei
星形胶质细胞是大脑回路不可或缺的组成部分。它们包裹突触，对神经元活动做出反应，并调节突触传递。星形胶质细胞是异质性的，在不同的回路中表现出不同的特征和功能。选择性地定位与给定神经元回路相关的星形胶质细胞将有助于阐明它们的回路特定功能，但到目前为止，这在技术上一直是一个挑战。最近，我们构建了基于黄热病疫苗YFV-17D的顺行跨神经元病毒载体。其中，如果YFVNS1基因在突触后神经元中表达，复制不能的ΔNS1Cre可以选择性地开启突触后神经元中的报告基因。在这里，我们发现，在突触后部位没有外源性表达的情况下，局部注射YFVΔNS1-Cre选择性地激活了下游脑区星形胶质细胞中的报告基因。星形胶质细胞的靶向可以发生在整个大脑中，但只针对追踪到的神经元回路。因此，YFVΔNS1-Cre为星形胶质细胞的选择性基因打靶提供了一种工具，以揭示其电路特异性作用。局部注射病毒示踪星形胶质细胞在全脑水平上星形胶质细胞示踪是神经元回路特异性限制性病毒复制将对星形胶质细胞的干扰降至最低可以从特定的神经细胞类型开始示踪星形胶质细胞是大脑中的一种主要细胞类型，星形胶质细胞是异质性的，在不同的回路中具有不同的功能。选择性地靶向与特定神经元回路相关的星形胶质细胞可以使研究电路特定的作用成为可能。这项研究提供了一种基于跨神经元病毒的靶向电路特异性星形胶质细胞的工具。星形胶质细胞是异质性的，在不同的神经元回路中发挥着不同的功能。然而，选择性地以回路特异性星形胶质细胞为靶点一直是具有挑战性的。在这里，汤普森等人。证明一种基于黄热病疫苗的病毒载体可以选择性地打开星形胶质细胞中与特定神经元投射相关的报告基因。
Astrocytes are integral components of brain circuitry. They enwrap synapses, react to neuronal activity, and regulate synaptic transmission. Astrocytes are heterogeneous and exhibit distinct features and functions in different circuits. Selectively targeting the astrocytes associated with a given neuronal circuit would enable elucidation of their circuit-specific functions but has been technically challenging to date. Recently, we constructed anterograde transneuronal viral vectors based on yellow fever vaccine YFV-17D. Among them, the replication-incompetent YFVΔNS1-Cre can selectively turn on reporter genes in postsynaptic neurons if the viral gene NS1 is expressed in postsynaptic neurons. Here we show that without exogenous expression of NS1 at the postsynaptic sites, locally injected YFVΔNS1-Cre selectively turns on reporter genes in astrocytes in downstream brain regions. The targeting of astrocytes can occur across the whole brain but is specific for the neuronal circuits traced. Therefore, YFVΔNS1-Cre provides a tool for selective genetic targeting of astrocytes to reveal their circuit-specific roles. Locally injected virus traces astrocytes at the whole-brain level Astrocyte tracing is neuronal circuit specific Restricted viral replication minimizes disturbance to astrocytes Tracing can be initiated from specific neuronal cell types Astrocytes, a major type of cells in the brain, are heterogeneous and have distinct functions in different circuits. Selective targeting of the astrocytes associated with specific neuronal circuits can enable investigation of circuit-specific roles. This study provides a tool for targeting circuit-specific astrocytes based on a transneuronal virus. Astrocytes are heterogeneous and exert distinct functions in different neuronal circuits. However, selectively targeting circuit-specific astrocytes has been challenging. Here, Thompson et al. demonstrate that a viral vector based on the yellow fever vaccine can selectively turn on reporter genes in the astrocytes associated with specific neuronal projections.
登录
查看更多内容
影响因子：
16.6
作者：
Lanjakornsiripan D;Pior BJ;Kawaguchi D;Furutachi S;Tahara T;Katsuyama Y;Suzuki Y;Fukazawa Y;Gotoh Y
通讯作者：
Gotoh Y
DOI：
10.1038/s41573-022-00390-x
发表时间：
2022-05
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
通讯作者：
--
影响因子：
25
作者：
Hasel, Philip;Rose, Indigo V. L.;Liddelow, Shane A.
通讯作者：
Liddelow, Shane A.
影响因子：
25
作者：
Armbruster, Moritz;Naskar, Saptarnab;Garcia, Jacqueline;Sommer, Mary;Kim, Elliot;Adam, Yoav;Haydon, Philip G.;Boyden, Edward S.;Cohen, Adam E.;Dulla, Chris G.
通讯作者：
Dulla, Chris G.
影响因子：
5.3
作者：
Bushong, EA;Martone, ME;Ellisman, MH
通讯作者：
Ellisman, MH