Optogenetic manipulation of neural circuits in awake marmosets
Optogenetic manipulation of neural circuits in awake marmosets
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DOI：
10.1152/jn.00197.2016
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发表时间：
2016-09-01
影响因子：
2.5
通讯作者：
Miller, Cory T.
中科院分区：
文献类型：
--
作者：
MacDougall, Matthew;Nummela, Samuel U.;Miller, Cory T.
光遗传学已经彻底改变了功能性神经元回路的研究（Boyden ES，Zhang F，班贝格E，内格尔G，Deisseroth K. Nat Neurosci 8：1263-1268，2005; Deisseroth K. Nat Methods 8：26-29，2011）。尽管这些技术在啮齿动物模型中应用最为成功，但它们在非人类灵长类动物大脑研究中也有可能产生类似的影响。普通绒猴（Callithrix jacchus）最近成为基因编辑的候选灵长类动物模型，为灵长类动物神经回路和疾病的研究提供了一个潜在的强大模型。在绒猴中应用病毒转导方法来识别和操纵神经元回路是开发该物种进行神经科学研究的关键一步。在本研究中，我们开发了一种新的，慢性的方法，成功地诱导快速的光刺激在个别皮层神经元转导腺相关病毒表达通道视紫红质（ChR 2）在清醒的绒猴。我们发现大部分神经元在病毒转导后可以被有效地光活化，并且这个过程可以重复几个月。这些数据表明，病毒转导和光学操纵的神经元群体的技术是适合的绒猴，并可以与现有的行为制剂的物种，以阐明功能性神经回路的感知和认知过程。
Optogenetics has revolutionized the study of functional neuronal circuitry (Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K. Nat Neurosci 8: 1263-1268, 2005; Deisseroth K. Nat Methods 8: 26-29, 2011). Although these techniques have been most successfully implemented in rodent models, they have the potential to be similarly impactful in studies of nonhuman primate brains. Common marmosets (Callithrix jacchus) have recently emerged as a candidate primate model for gene editing, providing a potentially powerful model for studies of neural circuitry and disease in primates. The application of viral transduction methods in marmosets for identifying and manipulating neuronal circuitry is a crucial step in developing this species for neuroscience research. In the present study we developed a novel, chronic method to successfully induce rapid photostimulation in individual cortical neurons transduced by adeno-associated virus to express channelrhodopsin (ChR2) in awake marmosets. We found that large proportions of neurons could be effectively photoactivated following viral transduction and that this procedure could be repeated for several months. These data suggest that techniques for viral transduction and optical manipulation of neuronal populations are suitable for marmosets and can be combined with existing behavioral preparations in the species to elucidate the functional neural circuitry underlying perceptual and cognitive processes.