1] Department of Dermatology, Columbia University, New York, New York 10032, USA [2].
1] Department of Dermatology, Columbia University, New York, New York 10032, USA [2] Graduate School of System Design and Management, Keio University, Yokohama 223-8526, Japan [3].
Nature. 2014 May 29;509(7502):617-21. doi: 10.1038/nature13250. Epub 2014 Apr 6.
Touch submodalities, such as flutter and pressure, are mediated by somatosensory afferents whose terminal specializations extract tactile features and encode them as action potential trains with unique activity patterns. Whether non-neuronal cells tune touch receptors through active or passive mechanisms is debated. Terminal specializations are thought to function as passive mechanical filters analogous to the cochlea's basilar membrane, which deconstructs complex sounds into tones that are transduced by mechanosensory hair cells. The model that cutaneous specializations are merely passive has been recently challenged because epidermal cells express sensory ion channels and neurotransmitters; however, direct evidence that epidermal cells excite tactile afferents is lacking. Epidermal Merkel cells display features of sensory receptor cells and make 'synapse-like' contacts with slowly adapting type I (SAI) afferents. These complexes, which encode spatial features such as edges and texture, localize to skin regions with high tactile acuity, including whisker follicles, fingertips and touch domes. Here we show that Merkel cells actively participate in touch reception in mice. Merkel cells display fast, touch-evoked mechanotransduction currents. Optogenetic approaches in intact skin show that Merkel cells are both necessary and sufficient for sustained action-potential firing in tactile afferents. Recordings from touch-dome afferents lacking Merkel cells demonstrate that Merkel cells confer high-frequency responses to dynamic stimuli and enable sustained firing. These data are the first, to our knowledge, to directly demonstrate a functional, excitatory connection between epidermal cells and sensory neurons. Together, these findings indicate that Merkel cells actively tune mechanosensory responses to facilitate high spatio-temporal acuity. Moreover, our results indicate a division of labour in the Merkel cell-neurite complex: Merkel cells signal static stimuli, such as pressure, whereas sensory afferents transduce dynamic stimuli, such as moving gratings. Thus, the Merkel cell-neurite complex is an unique sensory structure composed of two different receptor cell types specialized for distinct elements of discriminative touch.
触觉亚模式,如颤动和压力,是由躯体感觉传入纤维介导的,其末端特化结构提取触觉特征,并将其编码为具有独特活动模式的动作电位列车。非神经元细胞通过主动还是被动机制来调节触觉感受器一直存在争议。末端特化结构被认为是被动机械滤波器,类似于耳蜗的基底膜,它将复杂的声音分解成音调,然后由机械感觉毛细胞进行转换。皮肤特化结构仅仅是被动的这一模型最近受到了挑战,因为表皮细胞表达感觉离子通道和神经递质;然而,缺乏表皮细胞兴奋触觉传入的直接证据。表皮 Merkel 细胞表现出感觉受体细胞的特征,并与慢适应型 I(SAI)传入纤维形成“突触样”接触。这些复合物编码空间特征,如边缘和纹理,定位于具有高触觉敏锐度的皮肤区域,包括须毛囊、指尖和触觉穹顶。在这里,我们证明 Merkel 细胞在小鼠中积极参与触觉接收。Merkel 细胞显示快速、触觉诱发的机械转导电流。完整皮肤中的光遗传学方法表明,Merkel 细胞是维持触觉传入纤维持续动作电位放电所必需的且充分的。缺乏 Merkel 细胞的触球传入纤维的记录表明,Merkel 细胞赋予了对动态刺激的高频响应能力,并实现了持续放电。这些数据是我们所知的,首次直接证明了表皮细胞和感觉神经元之间存在功能性、兴奋性连接。总的来说,这些发现表明 Merkel 细胞主动调节机械感觉反应,以提高高时空分辨率。此外,我们的结果表明,在 Merkel 细胞-神经突复合物中存在分工:Merkel 细胞传递静态刺激,如压力,而感觉传入纤维则传递动态刺激,如移动光栅。因此,Merkel 细胞-神经突复合物是一种独特的感觉结构,由两种不同的受体细胞类型组成,专门用于区分触觉的不同元素。