Neuroanatomy goes viral!
Neuroanatomy goes viral!
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DOI：
10.3389/fnana.2015.00080
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发表时间：
2015
影响因子：
2.9
通讯作者：
Beier KT
中科院分区：
文献类型：
--
作者：
Nassi JJ;Cepko CL;Born RT;Beier KT
神经系统之所以复杂，不仅是因为它含有大量的神经元，而且还因为它们之间的连接具有特殊性。揭示这种特殊性是神经解剖学的任务。在这一努力中，神经解剖学家传统上利用了一系列令人印象深刻的工具，从高尔基方法到电子显微镜。研究解剖学的理想方法是标记互连的神经元，此外，还允许在这些神经元中表达外源基因。幸运的是，大自然已经以嗜神经病毒的形式部分开发了这种方法，这种病毒已经进化到可以在突触连接的神经元之间传递遗传物质，同时在很大程度上避开神经胶质细胞和免疫系统。虽然这些特征使其中一些病毒对人类健康构成威胁，但简单的修改使它们可以在受控实验环境中使用，从而使神经解剖学家能够追踪大脑区域内和大脑区域之间的多突触连接。野生型嗜神经病毒，例如狂犬病病毒和α-疱疹病毒，已经为我们对大脑连接的理解做出了巨大贡献，现代分子技术已经能够构建这些病毒和其他病毒的重组形式。这些新设计的试剂特别有用，因为它们可以针对基因定义的神经元群体，仅将一个突触传播到输入或输出，并携带指令，通过这些指令可以使目标神经元表达外源蛋白质，例如钙传感器或光敏离子通道，可用于研究神经元功能。在这篇综述中，我们讨论了神经解剖学家工具箱中已经存在的病毒的这些独特的强大特征，以及目前限制其实用性的生物学方面。基于后者，我们考虑通过降低毒性、改善突触传播的控制以及扩大可研究的物种范围来改进病毒追踪方法的策略。
The nervous system is complex not simply because of the enormous number of neurons it contains but by virtue of the specificity with which they are connected. Unraveling this specificity is the task of neuroanatomy. In this endeavor, neuroanatomists have traditionally exploited an impressive array of tools ranging from the Golgi method to electron microscopy. An ideal method for studying anatomy would label neurons that are interconnected, and, in addition, allow expression of foreign genes in these neurons. Fortuitously, nature has already partially developed such a method in the form of neurotropic viruses, which have evolved to deliver their genetic material between synaptically connected neurons while largely eluding glia and the immune system. While these characteristics make some of these viruses a threat to human health, simple modifications allow them to be used in controlled experimental settings, thus enabling neuroanatomists to trace multi-synaptic connections within and across brain regions. Wild-type neurotropic viruses, such as rabies and alpha-herpes virus, have already contributed greatly to our understanding of brain connectivity, and modern molecular techniques have enabled the construction of recombinant forms of these and other viruses. These newly engineered reagents are particularly useful, as they can target genetically defined populations of neurons, spread only one synapse to either inputs or outputs, and carry instructions by which the targeted neurons can be made to express exogenous proteins, such as calcium sensors or light-sensitive ion channels, that can be used to study neuronal function. In this review, we address these uniquely powerful features of the viruses already in the neuroanatomist’s toolbox, as well as the aspects of their biology that currently limit their utility. Based on the latter, we consider strategies for improving viral tracing methods by reducing toxicity, improving control of transsynaptic spread, and extending the range of species that can be studied.
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影响因子：
12.4
作者：
Cearley, CN;Wolfe, JH
通讯作者：
Wolfe, JH
影响因子：
2.7
作者：
Beier, Kevin T.;Samson, Maria Elena S.;Cepko, Constance L.
通讯作者：
Cepko, Constance L.
影响因子：
--
作者：
Card, J Patrick;Enquist, Lynn W
通讯作者：
Enquist, Lynn W
影响因子：
3.7
作者：
Ahmed, M;Lyles, DS
通讯作者：
Lyles, DS
影响因子：
16.2
作者：
Arenkiel, Benjamin R.;Peca, Joao;Feng, Guoping
通讯作者：
Feng, Guoping