Getting a Foot IN the Door: GABAergic INterneuron-Specific Enhancers.
Getting a Foot IN the Door: GABAergic INterneuron-Specific Enhancers.
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Getting a Foot IN the Door：GABA能神经元特异性增强子。
DOI：
10.1177/1535759720985841
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发表时间：
2021-03
影响因子：
3.6
通讯作者：
Goldberg EM
中科院分区：
文献类型：
--
作者：
Goldberg EM
Viral Manipulation of Functionally Distinct Interneurons in Mice，Non-Human Primates and Humans Vormstein-Schneider D，Lin JD，Pelkey KA，Chittajallu R，Guo B，Arias-Garcia MA，Allaway K，Sakopoulos S，Schneider G，史蒂文森O，Vergara J，Sharma J，Zhang Q，弗兰肯TP，Smith J，Ibrahim LA，Mastro KJ，Sabri E，Huang S，Favuzzi E，Burbridge T，Xu Q，Guo L，Vogel I，Sanchez V，Saldi GA，Gorissen BL，Yuan X，Zaghloul KA，Devinsky O，Sabatini BL，Batista-Brito R，Reynolds J，Feng G，Fu Z，McBain CJ，Fishell G，Dimidschstein J. Nat Neurosci. 2020;23（12）：1629-1636. doi：10.1038/s41593-020-0692-9最近在重组腺相关病毒载体背景下成功鉴定基因调节元件，实现了细胞类型限制的基因表达。然而，在大脑皮层内，这些工具在很大程度上限于广泛的神经元类别。为了克服这一局限性，我们开发了一种策略，导致多个新的增强子的目标功能不同的神经元亚型的鉴定。通过研究疾病基因Scn 1a的调控景观，我们发现了对小清蛋白（PV）和血管活性肠肽表达中间神经元有选择性的增强子。证明这些元素的功能效用，我们表明，PV特异性增强子允许选择性靶向和操纵这些神经元跨越脊椎动物物种，包括人类。最后，我们证明了我们的选择方法是可推广的，并在不同的大脑区域内以精致的特异性表征额外的PV特异性增强子。总而言之，这些病毒工具可用于细胞类型特异性电路操作，并在治疗干预中具有相当大的前景。
Viral Manipulation of Functionally Distinct Interneurons in Mice, Non-Human Primates and Humans Vormstein-Schneider D, Lin JD, Pelkey KA, Chittajallu R, Guo B, Arias-Garcia MA, Allaway K, Sakopoulos S, Schneider G, Stevenson O, Vergara J, Sharma J, Zhang Q, Franken TP, Smith J, Ibrahim LA, Mastro KJ, Sabri E, Huang S, Favuzzi E, Burbridge T, Xu Q, Guo L, Vogel I, Sanchez V, Saldi GA, Gorissen BL, Yuan X, Zaghloul KA, Devinsky O, Sabatini BL, Batista-Brito R, Reynolds J, Feng G, Fu Z, McBain CJ, Fishell G, Dimidschstein J. Nat Neurosci. 2020;23(12):1629-1636. doi:10.1038/s41593-020-0692-9 Recent success in identifying gene-regulatory elements in the context of recombinant adeno-associated virus vectors has enabled cell-type-restricted gene expression. However, within the cerebral cortex, these tools are largely limited to broad classes of neurons. To overcome this limitation, we developed a strategy that led to the identification of multiple new enhancers to target functionally distinct neuronal subtypes. By investigating the regulatory landscape of the disease gene Scn1a, we discovered enhancers selective for parvalbumin (PV) and vasoactive intestinal peptide-expressing interneurons. Demonstrating the functional utility of these elements, we show that the PV-specific enhancer allowed for the selective targeting and manipulation of these neurons across vertebrate species, including humans. Finally, we demonstrate that our selection method is generalizable and characterizes additional PV-specific enhancers with exquisite specificity within distinct brain regions. Altogether, these viral tools can be used for cell type–specific circuit manipulation and hold considerable promise for use in therapeutic interventions.
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影响因子：
46.9
作者：
Chen R;Gore F;Nguyen QA;Ramakrishnan C;Patel S;Kim SH;Raffiee M;Kim YS;Hsueh B;Krook-Magnusson E;Soltesz I;Deisseroth K
通讯作者：
Deisseroth K
影响因子：
16.6
作者：
通讯作者：
--
影响因子：
7.7
作者：
Hrvatin, Sinisa;Tzeng, Christopher P.;Greenberg, Michael E.
通讯作者：
Greenberg, Michael E.
影响因子：
64.8
作者：
Krienen FM;Goldman M;Zhang Q;C H Del Rosario R;Florio M;Machold R;Saunders A;Levandowski K;Zaniewski H;Schuman B;Wu C;Lutservitz A;Mullally CD;Reed N;Bien E;Bortolin L;Fernandez-Otero M;Lin JD;Wysoker A;Nemesh J;Kulp D;Burns M;Tkachev V;Smith R;Walsh CA;Dimidschstein J;Rudy B;S Kean L;Berretta S;Fishell G;Feng G;McCarroll SA
通讯作者：
McCarroll SA
丘脑的闭环光遗传学控制是在皮质损伤后中断癫痫发作的工具。
影响因子：
25
作者：
Paz, Jeanne T.;Davidson, Thomas J.;Frechette, Eric S.;Delord, Bruno;Parada, Isabel;Peng, Kathy;Deisseroth, Karl;Huguenard, John R.
通讯作者：
Huguenard, John R.