Interrogating the mouse thalamus to correct human neurodevelopmental disorders.
Interrogating the mouse thalamus to correct human neurodevelopmental disorders.
复制标题
询问小鼠丘脑以纠正人类神经发育障碍。
DOI：
10.1038/mp.2016.183
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发表时间：
2017-02
影响因子：
11
通讯作者：
Halassa MM
中科院分区：
文献类型：
--
作者：
Schmitt LI;Halassa MM
虽然定位感觉和运动缺陷是临床神经病学的基石之一，但精神病学的行为和认知缺陷仍然不受这种方法的影响。在精神病学中，主要的挑战包括神经回路受到干扰的相对微妙之处，以及对基本回路功能与思想和行为之间的关系的有限理解。神经发育障碍为解决第一个挑战提供了一个窗口，因为它们具有强大的遗传基础，可以与生物机制联系起来。这种联系得益于小鼠的遗传模型，在这篇综述中，我们强调了这种小型哺乳动物现在是如何让我们破解神经回路的。我们回顾了最近对小鼠丘脑的研究，讨论了它们如何揭示了可能构成人类感知和注意力的一般原理。控制丘脑感觉反应的大小（增益）是一种注意机制，小鼠以前所未有的分辨率使其功能解剖成为可能。此外，在小鼠身上建立人类遗传神经发育疾病模型显示了丘脑增益控制的减少如何导致注意力缺陷。这为我们如何解开精神疾病的复杂性开辟了新的领域；通过机械解剖丘脑回路，老鼠不仅让我们了解了它们的基本工作原理，还让我们了解了它们的功能障碍是如何精确地映射到行为和认知缺陷上的。未来的研究有望取得更大的进展，希望有原则地靶向已确定的丘脑回路可以具有独特的治疗效果。
While localizing sensory and motor deficits is one of the cornerstones of clinical neurology, behavioral and cognitive deficits in psychiatry remain impervious to this approach. In psychiatry, major challenges include the relative subtlety by which neural circuits are perturbed, and the limited understanding of how basic circuit functions relate to thought and behavior. Neurodevelopmental disorders offer a window to addressing the first challenge given their strong genetic underpinnings, which can be linked to biological mechanisms. Such links have benefited from genetic modeling in the mouse, and in this review we highlight how this small mammal is now allowing us to crack neural circuits as well. We review recent studies of mouse thalamus, discussing how they revealed general principles that may underlie human perception and attention. Controlling the magnitude (gain) of thalamic sensory responses is a mechanism of attention, and the mouse has enabled its functional dissection at an unprecedented resolution. Further, modeling human genetic neurodevelopmental disease in the mouse has shown how diminished thalamic gain control can lead to attention deficits. This breaks new ground in how we untangle the complexity of psychiatric diseases; by making thalamic circuits accessible to mechanistic dissection, the mouse has not only taught us how they fundamentally work, but also how their dysfunction can be precisely mapped onto behavioral and cognitive deficits. Future studies promise even more progress, with the hope that principled targeting of identified thalamic circuits can be uniquely therapeutic.