Merkel Cells Activate Sensory Neural Pathways Through Adrenergic Synapses. Hoffman et al

Epithelial-neuronal signaling is essential for sensory encoding in touch, itch and nociception; however, little is known about the release mechanisms and neurotransmitter receptors through which skin cells govern neuronal excitability. Merkel cells are mechanosensory epidermal cells that have long been proposed to activate neuronal afferents through chemical synaptic transmission. We employed a set of classical criteria for chemical neurotransmission as framework to test this hypothesis. RNA sequencing of adult mouse Merkel cells demonstrated that they express presynaptic molecules and biosynthetic machinery for adrenergic transmission. Moreover, live-cell imaging directly demonstrated that Merkel cells mediate activity- and VMAT-dependent release of fluorescent catecholamine neurotransmitter analogues. Touch-evoked firing in Merkel-cell afferents was inhibited either by pre-synaptic silencing of SNARE-mediated vesicle release from Merkel cells or by neuronal deletion of beta2-adrenergic receptors. Together, these results identify both pre- and postsynaptic mechanisms through which Merkel cells excite mechanosensory afferents to encode gentle touch. (Abstract from Hoffman et al., 2018, Neuron) Version 2.0: An earlier draft of "H&18_Source_data_Suppl_Figs" was inadvertently uploaded. A corrected file has been updated.上皮-神经元信号传导对于触觉、瘙痒及伤害性感受的感觉编码至关重要；然而，目前学界对皮肤细胞调控神经元兴奋性的释放机制与神经递质受体仍知之甚少。梅克尔细胞（Merkel cells）是一类机械感觉性表皮细胞，长期以来被推测可通过化学突触传递激活神经元传入纤维。本研究以化学神经传递的一系列经典标准作为验证框架，对该假说展开检验。对成年小鼠梅克尔细胞的RNA测序（RNA sequencing）结果显示，其表达肾上腺素能传递所需的突触前分子与生物合成机制。此外，活细胞成像（live-cell imaging）实验直接证实，梅克尔细胞可介导依赖于活动状态与VMAT的荧光儿茶酚胺类神经递质类似物释放。通过沉默梅克尔细胞内SNARE介导的囊泡释放以实现突触前抑制，或是敲除神经元内的β2-肾上腺素能受体（beta2-adrenergic receptors），均可抑制梅克尔细胞传入纤维的触觉诱发放电。综上，本研究明确了梅克尔细胞激活机械感觉传入纤维以编码轻柔触觉的突触前与突触后机制。（节选自Hoffman等2018年发表于《Neuron》的研究摘要） 版本2.0：此前不慎上传了《H&18_Source_data_Suppl_Figs》的初稿，现已更新修正后的版本。