Nature展现大脑中的平衡艺术

　　

生物通报道：加州大学圣迭戈医学院的科学家们，发现了大脑维持内部平衡的一个基础机制，这一成果于六月二十二日提前发表在Nature杂志的网站上。

大脑中的神经元会收到大量来自兴奋神经元的刺激信号，同时也会收到抑制神经元发送的信号。研究人员指出， 对于接收信号的单个神经元而言，这两种信号的总量需要保持一个恒定的比例，即E/I比。

研究显示，在小鼠大脑皮层的神经元中，给定时间的E/I比是一个常数。由于哺乳动物的大脑基础结构在种属之间高度保守，很可能人类大脑也存在着这样的情况。

“大脑中的神经元同时受到刹车和加速装置的控制，”文章的共同作者，Massimo Scanziani教授说。“也就是说，你不可能纯粹通过兴奋性神经元或抑制性神经元来进行刺激。”

“兴奋性信号和抑制性信号处于一场拉锯战中，这虽然看起来很奇怪，但实际上却非常巧妙。在此基础上，大脑能够极其微妙地控制神经元对刺激的应答。”Scanziani说。举例来说，刺激和抑制一直彼此关联，就可以避免神经元出现永久性活化或沉默（抑制）。

研究人员通过实验揭示了，大脑维持E/I比的具体机制。他们发现，这种调控是由抑制性神经元执行的，抑制性神经元会根据兴奋性刺激，适当地增强或削弱抑制性突触。突触是两个神经元之间的连接处，信号在此处被放大的程度就是突触强度。

“我们的研究显示，抑制性神经元是大脑中的主要调控者，负责确保抑制性突触与细胞收到的兴奋性刺激相匹配，”Scanziani解释道。举例来说，如果一个神经细胞收到的兴奋性刺激加倍了，那么在几天内抑制性突触的强度也会随之翻番。（延伸阅读：Nature重大成果：新技术展现透明的完整大脑）

研究人员认为，自闭症、癫痫和精神分裂症等神经疾病都与大脑保持理想E/I比的能力有关。此外，帕金森症、亨廷顿舞蹈病等一些神经退行性疾病，也很可能与E/I平衡发生改变有关。

“E/I平衡被打破，会完全改变我们对世界的感知，”Scanziani说。“我们将无法正确调节和适应日常生活中的各种刺激。E/I失衡最容易在社交互动中引起注意，因为社交活动需要特别微妙的神经元调节。”

研究的第一作者Minghan Xue指出，“现在我们知道了正常到脑调控E/I平衡的具体机制，可以着手解决疾病状态中出现的相关问题，为通过治疗手段恢复大脑平衡奠定基础。”

 

生物通编辑：叶予

生物通推荐原文摘要：

Equalizing excitation–inhibition ratios across visual cortical neurons

The relationship between synaptic excitation and inhibition (E/I ratio), two opposing forces in the mammalian cerebral cortex, affects many cortical functions such as feature selectivity and gain1, 2. Individual pyramidal cells show stable E/I ratios in time despite fluctuating cortical activity levels. This is because when excitation increases, inhibition increases proportionally through the increased recruitment of inhibitory neurons, a phenomenon referred to as excitation–inhibition balance3, 4, 5, 6, 7, 8, 9. However, little is known about the distribution of E/I ratios across pyramidal cells. Through their highly divergent axons, inhibitory neurons indiscriminately contact most neighbouring pyramidal cells10, 11. Is inhibition homogeneously distributed12 or is it individually matched to the different amounts of excitation received by distinct pyramidal cells? Here we discover that pyramidal cells in layer 2/3 of mouse primary visual cortex each receive inhibition in a similar proportion to their excitation. As a consequence, E/I ratios are equalized across pyramidal cells. This matched inhibition is mediated by parvalbumin-expressing but not somatostatin-expressing inhibitory cells and results from the independent adjustment of synapses originating from individual parvalbumin-expressing cells targeting different pyramidal cells. Furthermore, this match is activity-dependent as it is disrupted by perturbing pyramidal cell activity. Thus, the equalization of E/I ratios across pyramidal cells reveals an unexpected degree of order in the spatial distribution of synaptic strengths and indicates that the relationship between the cortex’s two opposing forces is stabilized not only in time but also in space.