Sohal Vikaas S, Zhang Feng, Yizhar Ofer, Deisseroth Karl
Department of Bioengineering, Stanford University, Stanford, California 94305, USA.
Nature. 2009 Jun 4;459(7247):698-702. doi: 10.1038/nature07991. Epub 2009 Apr 26.
Synchronized oscillations and inhibitory interneurons have important and interconnected roles within cortical microcircuits. In particular, interneurons defined by the fast-spiking phenotype and expression of the calcium-binding protein parvalbumin have been suggested to be involved in gamma (30-80 Hz) oscillations, which are hypothesized to enhance information processing. However, because parvalbumin interneurons cannot be selectively controlled, definitive tests of their functional significance in gamma oscillations, and quantitative assessment of the impact of parvalbumin interneurons and gamma oscillations on cortical circuits, have been lacking despite potentially enormous significance (for example, abnormalities in parvalbumin interneurons may underlie altered gamma-frequency synchronization and cognition in schizophrenia and autism). Here we use a panel of optogenetic technologies in mice to selectively modulate multiple distinct circuit elements in neocortex, alone or in combination. We find that inhibiting parvalbumin interneurons suppresses gamma oscillations in vivo, whereas driving these interneurons (even by means of non-rhythmic principal cell activity) is sufficient to generate emergent gamma-frequency rhythmicity. Moreover, gamma-frequency modulation of excitatory input in turn was found to enhance signal transmission in neocortex by reducing circuit noise and amplifying circuit signals, including inputs to parvalbumin interneurons. As demonstrated here, optogenetics opens the door to a new kind of informational analysis of brain function, permitting quantitative delineation of the functional significance of individual elements in the emergent operation and function of intact neural circuitry.
同步振荡和抑制性中间神经元在皮层微回路中具有重要且相互关联的作用。特别是，由快速放电表型和钙结合蛋白小白蛋白的表达所定义的中间神经元被认为参与了γ（30 - 80赫兹）振荡，据推测这种振荡可增强信息处理。然而，由于小白蛋白中间神经元无法被选择性控制，尽管其潜在意义重大（例如，小白蛋白中间神经元的异常可能是精神分裂症和自闭症中γ频率同步改变及认知改变的基础），但一直缺乏对其在γ振荡中功能意义的确定性测试，以及对小白蛋白中间神经元和γ振荡对皮层回路影响的定量评估。在这里，我们使用一组光遗传学技术在小鼠中单独或组合地选择性调节新皮层中的多个不同回路元件。我们发现抑制小白蛋白中间神经元会在体内抑制γ振荡，而驱动这些中间神经元（即使通过无节律的主细胞活动）足以产生新出现的γ频率节律性。此外，发现对兴奋性输入的γ频率调制反过来通过降低回路噪声和放大回路信号（包括对小白蛋白中间神经元的输入）来增强新皮层中的信号传输。如此处所示，光遗传学为脑功能的一种新型信息分析打开了大门，允许对完整神经回路的新出现的运作和功能中各个元件的功能意义进行定量描述。
