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A Novel Retrograde AAV Variant for Functional Manipulation of Cortical Projection Neurons in Mice and Monkeys
Neuroscience Bulletin ( IF 5.9 ) Pub Date : 2023-07-11 , DOI: 10.1007/s12264-023-01091-0
Yefei Chen 1, 2 , Jingyi Wang 2, 3 , Jing Liu 1, 2 , Jianbang Lin 2, 3 , Yunping Lin 2 , Jinyao Nie 2 , Qi Yue 2 , Chunshan Deng 2, 3, 4, 5 , Xiaofei Qi 1 , Yuantao Li 1, 6 , Ji Dai 2, 3, 4, 5 , Zhonghua Lu 2, 3, 4, 5, 7
Affiliation  

Retrograde adeno-associated viruses (AAVs) are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural networks. However, few retrograde AAV capsids have been shown to offer access to cortical projection neurons across different species and enable the manipulation of neural function in non-human primates (NHPs). Here, we report the development of a novel retrograde AAV capsid, AAV-DJ8R, which efficiently labeled cortical projection neurons after local administration into the striatum of mice and macaques. In addition, intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral alterations. Moreover, AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque putamen. These data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.



中文翻译:


一种新型逆行 AAV 变体,用于小鼠和猴子皮质投射神经元的功能操作



逆行腺相关病毒(AAV)能够感染投射神经元的轴突,并作为神经网络解剖和功能表征的强大工具。然而,很少有逆行 AAV 衣壳被证明可以进入不同物种的皮质投射神经元,并能够操纵非人类灵长类动物 (NHP) 的神经功能。在这里,我们报告了一种新型逆行 AAV 衣壳 AAV-DJ8R 的开发,该衣壳在局部给药至小鼠和猕猴的纹状体后,可有效标记皮质投射神经元。此外,纹状体内注射的 AAV-DJ8R 介导小鼠运动皮层中的视蛋白表达并诱导强烈的行为改变。此外,病毒递送至猕猴壳核后,AAV-DJ8R 显着增加了运动皮质神经元在光遗传学光刺激下的放电。这些数据证明了 AAV-DJ8R 作为啮齿动物和 NHP 皮质投射神经元的有效逆行示踪剂的有用性,并表明其适用于进行功能询问。

更新日期:2023-07-11
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