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)

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表皮神经元信号在触觉、瘙痒和痛觉的感官编码中至关重要；然而，关于皮肤细胞通过何种释放机制和神经递质受体来调控神经元兴奋性的知识却鲜为人知。默克尔细胞作为机械感受性表皮细胞，长期以来一直被认为可以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经典标准作为框架，以验证这一假设。成年小鼠默克尔细胞的RNA测序结果表明，它们表达突触前分子和肾上腺素能传递的生物合成机制。此外，活细胞成像直接证实默克尔细胞介导活动依赖性和VMAT依赖性的荧光儿茶酚胺神经递质类似物的释放。触觉诱发的默克尔细胞传入纤维放电可以通过两种机制被抑制：一是通过预先沉默默克尔细胞中SNARE介导的囊泡释放，二是通过神经元中β2-肾上腺素受体的删除。综上所述，这些结果确定了默克尔细胞通过突触前和突触后机制兴奋机械感受性传入纤维以编码轻触觉的途径。（Hoffman等人，2018年，《神经元》）