J. Neurosci连发两篇中科院学者研究新成果

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生物通报道：《神经学杂志》（Journal of Neuroscience）影响因子7.12，是神经科学会旗下的神经科学研究领域的高水平杂志。近期中科院动物研究所以及生物物理所的两个研究组分别在此刊物上发表文章，解析了神经干细胞调控，以及脑神经活动方面的新成果。
' ^# z" w1 o$ M7 k5 u来自动物研究所的焦建伟研究组发现Ezh2被敲除后，短期记忆受到明显的影响，揭示Ezh2在小鼠在短期空间记忆中发挥重要作用。
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了解人类大脑，揭开学习与记忆的奥秘是事关人类健康战略的核心任务之一。成年大脑海马等区域存在神经干细胞，这些神经干细胞经过增殖、分化后整合到特定的学习和记忆神经环路中，探索成年大脑神经干细胞的调控机制是理解学习和记忆的分子细胞基础。然而目前对于表观遗传分子如何参与调控成年神经干细胞的增殖和分化以及具体的机制还具有相当大的空白。
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3 Q# f: Y. F$ l( u! R: B& |# U研究组前期芯片结果显示组蛋白H3K27甲基转移酶Ezh2在成年神经干细胞/前体细胞中高表达，进一步的免疫组化分析Ezh2定位在神经前体细胞。体外实验表明Ezh2敲除后，神经球的数量和大小均有不同程度的减少，体内实验表明Ezh2敲除后，通过BrdU标记的神经细胞增殖受到明显的抑制。
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进一步的机制实验表明，Ezh2通过增加组蛋白H3K27的甲基化，抑制Pten蛋白的表达，影响Akt/mTOR信号通路，从而调控神经干细胞及神经元的产生。通过水迷宫，八臂迷宫等多种先进的行为学实验及模型，科研人员发现Ezh2被敲除后，短期记忆受到明显的影响，揭示Ezh2在小鼠在短期空间记忆中发挥重要作用。该研究可以提高人们对于表观遗传分子如何调控神经干细胞增殖和分化机制的理解，为更好探索学习与记忆提供理论基础，并有可能为未来推动干细胞面向转化应用提供重要的理论依据。 9 ]5 T, q( y+ I5 ]! s# R0 \+ s

; L: |- Y& P  W另外一篇文章中，生物物理研究所脑与认知国家重点实验室脑成像团队罗欢研究员和周可研究员采用高时间分辨率方式来研究注意行为的动态时间组织过程，取得了时间组织领域的重要成果。
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4 `  E  Y* |; V  `' @, d4 ]传统认为，即使脑神经活动在时间上是快速变化的，认知行为（各种认知任务指标，包括正确率、反映时等）反映的仍然一般都是一个较为缓慢的过程。
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这项研究采用高时间分辨率方式来研究注意行为的动态时间组织过程，发现：（1）经典的空间注意行为表现在这个动态过程的低频段上；（2）空间注意行为包含大量动态振荡成分（包括10Hz alpha 频段等）；（3）空间注意行为的很多动态特性都和以往电生理记录中的动态振荡特征一致（例如低频段和高频段的耦合等）。 ' n+ G0 Q" S9 T: M3 c# A
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这一发现的意义在于：（1）表明传统认知行为测量的只是“冰山一角”，反映的只是慢的变化成分，而认知行为实际是包含大量动态特征可能直接反映神经活动；（2）提出了一种多物体表征的神经机制：两个空间位置是由~10Hz alpha 脉冲的振荡方式在时间上交替采样的，反映了一种基于时间组织（神经振荡）的空间组织（多空间位置同时表征）的神经机制。 　
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Behavioral Oscillations in Attention: Rhythmic α Pulses Mediated through θ Band
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Neuronal oscillations are ubiquitous in the brain and contribute to perception and attention. However, most associated evidence derives from post hoc correlations between brain dynamics and behavior. Although a few recent studies demonstrate rhythms in behavior, it remains largely unknown whether behavioral performances manifest spectrotemporal dynamics in a neurophysiologically relevant manner (e.g., the temporal modulation of ongoing oscillations, the cross-frequency coupling). To investigate the issue, we examined fine spectrotemporal dynamics of behavioral time courses in a large sample of human participants (n = 49), by taking a high time-resolved psychophysical measurement in a precuing attentional task. We observed compelling dynamic oscillatory patterns directly in behavior. First, typical attentional effects are demonstrated in low-pass (0?2 Hz) filtered time courses of behavioral responses. Second, an uninformative peripheral cue elicits recurring α-band (8?20 Hz) pulses in behavioral performances, and the elicited α pulses for cued and uncued conditions are in a temporally alternating relationship. Finally, ongoing α-band power is phase locked to ongoing θ-bands (3?5 Hz) in behavioral time courses. Our findings constitute manifestation of oscillations at physiologically relevant rhythms and power-phase locking, as widely observed in neurophysiological recordings, in behavior. The findings suggest that behavioral performance actually consists of rich dynamic information and may reflect underlying neuronal oscillatory substrates. Our data also speak to a neural mechanism for item attention based on successive cycles (θ) of a sequential attentional sampling (α) process. ) L. C6 p% b9 K

6 @/ `# f% x- J* ?& mEzh2 Regulates Adult Hippocampal Neurogenesis and Memory& k' C/ b) i! Y6 c

$ W  q; Y6 `+ v: Z9 _Adult neurogenesis is thought to be crucial for preserving cognitive functions, which is tightly controlled by various epigenetic regulators. As the methyltransferase of histone H3K27, the role of Ezh2 in neurogenesis of adult mice and its mechanism of action are largely unknown. Here, we show that Ezh2 is expressed in actively dividing neural stem cells (NSCs)/progenitor cells as well as mature neurons, but not in quiescent NSCs in the subgranular zone. The deletion of Ezh2 in NSCs/progenitor cells results in a reduction in progenitor cell proliferation. Furthermore, we found that Ezh2 regulates progenitor cell proliferation by suppressing Pten expression and promoting the activation of Akt-mTOR. Moreover, the loss of Ezh2 in progenitor cells leads to a decrease in the number of neurons, which was observed by long-term tracing. Strikingly, conditional knockout of Ezh2 ultimately results in impairments in spatial learning and memory, contextual fear memory, and pattern separation. Our findings demonstrate the essential role of Ezh2 in the proliferation of progenitor cells, thus providing insight into the molecular mechanisms of adult neurogenesis in preserving cognitive functions.
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