Neurocircuits to Behavior: The New Revolution.
Neurocircuits to Behavior: The New Revolution.
复制标题
行为神经回路：新革命。
DOI：
10.1097/hrp.0000000000000152
复制
发表时间：
2017
影响因子：
3.8
通讯作者：
Ressler,KerryJ
中科院分区：
文献类型：
--
作者：
Ressler,KerryJ
光遗传学——通过基因控制、分子工程、光敏离子通道控制神经元放电——在过去十年中真正改变了神经科学。虽然有一些人因其发现和初步实施而受到赞誉，但斯坦福大学的精神病医生科学家 Karl Deisseroth 被广泛认为是这些用于剖析与行为相关的神经回路的技术的创新和传播的核心人物（Boyden 等人[2005]；6 Deisseroth [2015] 7）。 几年前，编码几种不同物种的基因 “视蛋白”（光敏）受体已在藻类和其他简单生物体中被发现。人们知道，其中一些受体可以在哺乳动物神经元中表达，不会产生不良后果，但是当某些波长的光（使用光纤技术）传递到这些神经元时，它们会激发动作电位。这些“兴奋性”光遗传学通道的最初版本是“通道视紫红质”家族的成员。与此同时，一组抑制通道被识别出来，最初属于“盐视紫红质”家族。自最初发现以来，许多其他蛋白质通道已被识别，从而产生了大量用于以精确方式控制神经元活动的特定工具。目前的疗法缺乏这种细胞或时间水平的精确度。例如，深部脑刺激对于治疗包括抑郁症在内的许多难治性神经精神综合症来说是一项强大的创新。然而，虽然这种刺激比 ECT 和经颅磁刺激更有针对性地针对神经回路，但从我们现在对神经区域内微回路的了解来看，这种刺激仍然是粗糙的。人们想象未来精神病学工具箱的可能性，其中包含驱动特定行为微电路的细胞类型特异性、光遗传学调节过程。
Optogenetics—the control of neuronal firing through genetically controlled, molecularly engineered, light-sensitive ion channels—has truly transformed neuroscience within the past decade. While several are credited with its discovery and initial implementation, Karl Deisseroth, a psychiatrist physicianscientist from Stanford, is widely regarded as being most central to the innovation and dissemination of these techniques for dissecting neural circuits related to behavior (Boyden et al.[2005]; 6 Deisseroth [2015] 7).Years earlier, genes encoding several different species of “opsin”(light-sensitive) receptors had been identified in algae and other simple organisms. It was known that some of these receptors could be expressed in mammalian neurons with no adverse consequences, but when certain wavelengths of light (using fiber-optic technology) were delivered to these neurons, they would fire action potentials. The initial versions of these “excitatory” optogenetic channels were members of the “channel rhodopsin” family. In parallel, a set of inhibitory channels were identified, initially of the “halorhodopsin” family. Since the initial discovery, many additional protein channels have been identified, leading to a large array of specific tools for controlling neuronal activity in precise ways. Current therapies lack such a cellular or temporal level of precision. Deep-brain stimulation, for example, has been a powerful innovation for a number of refractory neuropsychiatric syndromes, including depression. Such stimulation, however, while much more targeted regionally to neural circuits than ECT and transcranial magnetic stimulation, is still crude from the perspective of what we now know about microcircuits within neural regions. One imagines the possibility of a future psychiatric toolbox of cell-type specific, optogenetically regulated processes that drive specific behavioral microcircuits.