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Merkel Cells Activate Sensory Neural Pathways through Adrenergic Synapses

Hoffman, Ben and Baba, Yoshichika and Griffith, Theanne and Masharov, Eugene and Woo, Seung and Roybal, Daniel and Karsenty, Gerard and Patapoutian, Ardem and Sulzer, David and Lumpkin, Ellen (2018) Merkel Cells Activate Sensory Neural Pathways through Adrenergic Synapses. Neuron, 100 (6). pp. 1401-1413. ISSN 10974199

Abstract

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 a 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 analogs. 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 β2-adrenergic receptors. Together, these results identify both pre- and postsynaptic mechanisms through which Merkel cells excite mechanosensory afferents to encode gentle touch.

Item Type: Article
Date Deposited: 22 Jan 2019 00:45
Last Modified: 22 Jan 2019 00:45
URI: https://oak.novartis.com/id/eprint/35278

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