Secrets of Meissner corpuscles The Meissner corpuscle, a mechanosensory end organ, was discovered more than 165 years ago and has since been found in the glabrous skin of all mammals, including that on human fingertips. Although prominently featured in textbooks, the function of the Meissner corpuscle is unknown. Neubarth et al. generated adult mice without Meissner corpuscles and used them to show that these corpuscles alone mediate behavioral responses to, and perception of, gentle forces (see the Perspective by Marshall and Patapoutian). Each Meissner corpuscle is innervated by two molecularly distinct, yet physiologically similar, mechanosensory neurons. These two neuronal subtypes are developmentally interdependent and their endings are intertwined within the corpuscle. Both Meissner mechanosensory neuron subtypes are homotypically tiled, ensuring uniform and complete coverage of the skin, yet their receptive fields are overlapping and offset with respect to each other. Science, this issue p. eabb2751; see also p. 1311 Light touch perception and fine sensorimotor control arise from spatially overlapping mechanoreceptors of the Meissner corpuscle. INTRODUCTION Meissner corpuscles are mechanosensory end organs that densely occupy mammalian glabrous skin. The basic anatomy of the Meissner corpuscle and the Aβ (large soma diameter and fast action potential conducting) mechanosensory neurons that innervate it have been widely described. However, little is known about the requirement for the Meissner corpuscle and its innervating Aβ mechanosensory neurons for touch-related behaviors, sensorimotor capabilities, and tactile perception. RATIONALE Mice lacking either brain-derived neurotrophic factor (BDNF) or its receptor TrkB have a range of developmental deficits, including an absence of Meissner corpuscles. We reasoned that confining TrkB manipulations to sensory neurons in conjunction with selective genetic labeling approaches would allow us to investigate the developmental assembly of Meissner corpuscles and their functions in somatosensation. While examining Meissner corpuscle development, we found that two Aβ mechanosensory neuron types innervate the corpuscle. Here, we assessed the requirement of Meissner corpuscles for touch sensitivity and fine sensorimotor control and the anatomical, physiological, and ultrastructural properties of the two Aβ sensory neurons that innervate this mechanosensory end organ. RESULTS Sensory neuron–specific knockout of TrkB resulted in complete loss of Meissner corpuscles without affecting other mechanosensory end organs in mouse glabrous (nonhairy) skin, including Aβ mechanosensory neuron–Merkel cell complexes and Pacinian corpuscles. Behavioral measurements showed that mice lacking Meissner corpuscles were deficient in perceiving and reacting to the gentlest detectable forces acting on glabrous skin and in fine sensorimotor control. Genetic labeling experiments revealed that Meissner corpuscles are innervated by two molecularly distinct Aβ sensory neuron types, one that expresses TrkB and the other that expresses the tyrosine kinase Ret. Despite innervating the same end organ, the responses of these two Aβ neuron types to tactile stimuli differed: The TrkB-positive (TrkB+) Meissner afferent was more sensitive and responded at both the onset and the offset of step indentations of glabrous skin, whereas the Ret+ Meissner afferent was less sensitive and rarely responded at step offset. Some Ret+ neurons even had sustained responses during a static indentation stimulus. In addition, the axonal endings of these two Aβ mechanosensory neuron types were found to be homotypically tiled but heterotypically offset. Computational modeling suggested that this anatomical arrangement maximizes information available for encoding acuity while ensuring complete coverage of the skin using a limited number of neurons. Finally, ultrastructural analysis using electron microscopy revealed that the axon terminals of the more sensitive TrkB+ Meissner afferents had greater numbers of lamellar cell wrappings than the terminals of the less sensitive Ret+ Meissner afferents. CONCLUSION We conclude that two homotypically tiled but heterotypically offset Aβ mechanosensory neurons with distinct molecular, physiological, and ultrastructural properties innervate Meissner corpuscles, which underlie the perception of, and behavioral responses to, the gentlest detectable forces acting on glabrous skin. Anatomy and physiology of Meissner corpuscles required for tactile behavior. (A to C) Meissner corpuscles and their Aβ afferents (A) were required for normal tactile sensitivity (B) and fine sensorimotor control (C). (D) TrkB+ and Ret+ Aβ neurons both innervated Meissner corpuscles. (E and F) TrkB+ Meissner afferents were more sensitive (E) and had more lamellar cell wrappings [(F), arrows indicate axons wrapped with lamellar processes] compared with Ret+ Meissner afferents. In (A), S100 and NFH are antibodies used to visualize Meissner corpuscles and their afferents, respectively. In (B) and (C), error bars represent SEM, and *p < 0.05, **p < 0.01, and ***p < 0.001. Meissner corpuscles are mechanosensory end organs that densely occupy mammalian glabrous skin. We generated mice that selectively lacked Meissner corpuscles and found them to be deficient in both perceiving the gentlest detectable forces acting on glabrous skin and fine sensorimotor control. We found that Meissner corpuscles are innervated by two mechanoreceptor subtypes that exhibit distinct responses to tactile stimuli. The anatomical receptive fields of these two mechanoreceptor subtypes homotypically tile glabrous skin in a manner that is offset with respect to one another. Electron microscopic analysis of the two Meissner afferents within the corpuscle supports a model in which the extent of lamellar cell wrappings of mechanoreceptor endings determines their force sensitivity thresholds and kinetic properties.

中文翻译：

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迈斯纳小体及其空间混合的传入是轻柔触觉的基础


迈斯纳小体的秘密 迈斯纳小体是一种机械感觉末端器官，被发现于 165 多年前，此后在所有哺乳动物的无毛皮肤中发现，包括人类指尖的皮肤。尽管迈斯纳小体在教科书中占有重要地位，但它的功能尚不清楚。纽巴特等人。生成了没有迈斯纳小体的成年小鼠，并用它们来证明这些小体单独介导对温和力量的行为反应和感知（参见马歇尔和帕塔普蒂安的观点）。每个迈斯纳小体都由两个分子上不同但生理上相似的机械感觉神经元支配。这两种神经元亚型在发育上是相互依赖的，它们的末端在小体内交织在一起。两种迈斯纳机械感觉神经元亚型都是同型平铺的，确保均匀且完整地覆盖皮肤，但它们的感受野相互重叠和偏移。科学，本期第 14 页。 eabb2751;另见 p. 1311 轻触感知和精细感觉运动控制源自迈斯纳小体空间重叠的机械感受器。简介 迈斯纳小体是密集占据哺乳动物无毛皮肤的机械感觉末端器官。迈斯纳小体和支配其的 Aβ（大胞体直径和快速动作电位传导）机械感觉神经元的基本解剖结构已被广泛描述。然而，人们对迈斯纳小体及其支配的 Aβ 机械感觉神经元对触摸相关行为、感觉运动能力和触觉感知的需求知之甚少。 基本原理 缺乏脑源性神经营养因子 (BDNF) 或其受体 TrkB 的小鼠存在一系列发育缺陷，包括缺乏迈斯纳小体。我们推断，将 TrkB 操作限制在感觉神经元上，并结合选择性基因标记方法，将使我们能够研究迈斯纳小体的发育组装及其在体感中的功能。在检查迈斯纳小体发育时，我们发现两种 Aβ 机械感觉神经元类型支配小体。在这里，我们评估了迈斯纳小体对触觉敏感性和精细感觉运动控制的需求，以及支配该机械感觉末端器官的两个 Aβ 感觉神经元的解剖学、生理学和超微结构特性。结果感觉神经元特异性敲除 TrkB 导致迈斯纳小体完全丧失，而不影响小鼠无毛（无毛）皮肤中的其他机械感觉终末器官，包括 Aβ 机械感觉神经元 - 默克尔细胞复合物和帕西尼小体。行为测量表明，缺乏迈斯纳小体的小鼠缺乏对作用在无毛皮肤上的最温和的可检测力的感知和反应，也缺乏精细的感觉运动控制。基因标记实验表明，迈斯纳小体由两种分子上不同的 Aβ 感觉神经元类型支配，一种表达 TrkB，另一种表达酪氨酸激酶 Ret。 尽管支配相同的终末器官，但这两种 Aβ 神经元类型对触觉刺激的反应不同：TrkB 阳性 (TrkB+) Meissner 传入神经更加敏感，并且对无毛皮肤的台阶凹痕的开始和偏移都有反应，而Ret+ Meissner 传入不太敏感，并且很少对步偏移做出反应。一些 Ret+ 神经元甚至在静态压痕刺激下也能产生持续的反应。此外，这两种 Aβ 机械感觉神经元类型的轴突末端被发现同型平铺但异型偏移。计算模型表明，这种解剖结构最大限度地提高了可用于编码敏锐度的信息，同时确保使用有限数量的神经元完全覆盖皮肤。最后，使用电子显微镜进行超微结构分析表明，较敏感的 TrkB+ Meissner 传入神经的轴突末端比不太敏感的 Ret+ Meissner 传入神经的轴突末端具有更多数量的层状细胞包裹。结论 我们得出的结论是，两个同型平铺但异型偏移的 Aβ 机械感觉神经元具有不同的分子、生理和超微结构特性，支配着迈斯纳小体，而迈斯纳小体是对作用在无毛皮肤上的最温和的可检测力的感知和行为反应的基础。触觉行为所需迈斯纳小体的解剖学和生理学。 (A 到 C) 迈斯纳小体及其 Aβ 传入神经 (A) 是正常触觉敏感性 (B) 和精细感觉运动控制 (C) 所必需的。 (D) TrkB+ 和 Ret+ Aβ 神经元均支配迈斯纳小体。 (E 和 F) 与 Ret+ Meissner 传入神经相比，TrkB+ Meissner 传入神经更敏感 (E) 并且具有更多的层状细胞包裹物 [(F)，箭头表示被层状突起包裹的轴突]。在 (A) 中，S100 和 NFH 是分别用于可视化迈斯纳小体及其传入神经的抗体。在 (B) 和 (C) 中，误差线代表 SEM，并且 *p < 0.05、**p < 0.01 和 ***p < 0.001。迈斯纳小体是密集占据哺乳动物无毛皮肤的机械感觉末端器官。我们培育了选择性缺乏迈斯纳小体的小鼠，发现它们在感知作用于无毛皮肤的最温和的可检测力和精细的感觉运动控制方面都存在缺陷。我们发现迈斯纳小体受到两种机械感受器亚型的支配，这两种机械感受器亚型对触觉刺激表现出不同的反应。这两种机械感受器亚型的解​​剖感受野以相对于彼此偏移的方式同质地平铺无毛皮肤。对红细胞内两个迈斯纳传入神经的电子显微镜分析支持了一个模型，其中机械感受器末端的层状细胞包裹程度决定了它们的力敏感性阈值和动力学特性。