Parvalbumin neurons and gamma rhythms enhance cortical circuit performance.
Parvalbumin neurons and gamma rhythms enhance cortical circuit performance.
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DOI：
10.1038/nature07991
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发表时间：
2009-06-04
期刊：
影响因子：
64.8
通讯作者：
Deisseroth, Karl
中科院分区：
文献类型：
--
作者：
Sohal, Vikaas S.;Zhang, Feng;Yizhar, Ofer;Deisseroth, Karl
同步振荡和抑制性中间神经元在皮质微电路中具有重要且相互关联的作用。特别是，由钙结合蛋白小清蛋白的快速尖峰表型和表达定义的中间神经元被认为参与伽玛（30-80 Hz）振荡，假设伽玛振荡可以增强信息处理。然而，由于小清蛋白中间神经元无法选择性控制，因此尽管具有潜在的巨大意义，但仍缺乏对其在伽马振荡中功能意义的明确测试，以及小清蛋白中间神经元和伽马振荡对皮质回路影响的定量评估（例如，小清蛋白中间神经元的异常可能是精神分裂症和自闭症中伽马频率同步和认知改变的基础）。在这里，我们在小鼠中使用一组光遗传学技术来选择性地单独或组合地调节新皮质中的多个不同的电路元件。我们发现抑制小清蛋白中间神经元会抑制体内的伽马振荡，而驱动这些中间神经元（即使通过非节律性主细胞活动）足以产生紧急的伽马频率节律性。此外，发现兴奋性输入的伽马频率调制反过来可以通过减少电路噪声和放大电路信号（包括小清蛋白中间神经元的输入）来增强新皮质的信号传输。正如此处所示，光遗传学为大脑功能的新型信息分析打开了大门，允许定量描述单个元素在完整神经回路的紧急操作和功能中的功能意义。
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.
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