Epidermal Merkel cells are mechanosensory cells that tune mammalian touch receptors

• Published in: Nature (London) Vol. 509; no. 7502; pp. 617 - 621
• Main Authors: Maksimovic, Srdjan, Nakatani, Masashi, Baba, Yoshichika, Nelson, Aislyn M., Marshall, Kara L., Wellnitz, Scott A., Firozi, Pervez, Woo, Seung-Hyun, Ranade, Sanjeev, Patapoutian, Ardem, Lumpkin, Ellen A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.05.2014; Nature Publishing Group
• Subjects: 13/106; 13/31; 13/51; 14/10; 14/19; 14/35; 45/77; 631/378/2620/2621; 64/60; 9/74; Action Potentials; Afferent Pathways; Animals; Basic Helix-Loop-Helix Transcription Factors - metabolism; Cells; Cellular biology; Electric Conductivity; Epidermal Cells; Epidermal growth factor; Epidermis - innervation; Female; Health aspects; Humanities and Social Sciences; Ion Channels - metabolism; letter; Male; Mechanotransduction, Cellular; Medical research; Merkel cells; Merkel Cells - metabolism; Mice; Models, Biological; multidisciplinary; Neurites - metabolism; Neurons; Neurons, Afferent - metabolism; Optogenetics; Physiological aspects; Pressure; Rodents; Science; Sensory perception; Skin; Touch - physiology; California; United States
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature13250

The cellular basis of touch has long been debated, in particular the relationship between sensory neurons and non-neuronal cells; a mouse study uses optogenetics to identify their distinct and collaborative roles, with skin-derived Merkel cells both transducing touch and actively tuning responses of touch-sensitive neurons. Non-neural Merkel cells stay in touch Merkel cells (also known as Merkel-Ranvier cells) are found in the vertebrate epidermis. They are non-neuronal but may make 'synapse-like' contact with neighbouring cells. It has been suggested that they are associated with the sensation of touch, but this has been difficult to prove and remains controversial. In this week's Nature two teams present clear evidence that Merkel cells are autonomous mechanosensors essential to fine touch perception. The cells express the mechanosensitive channel Piezo2, which allows them to actively tune somatosensory neurons' responses to touch. These results are consistent with a compound receptor system model in which epidermal cells help neurons to discriminate between different types of touch — such as flutter, stretch and pressure — and therefore to decode the fine details of objects. 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 1 . 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 2 , 3 ; however, direct evidence that epidermal cells excite tactile afferents is lacking. Epidermal Merkel cells display features of sensory receptor cells 4 , 5 and make ‘synapse-like’ contacts 5 , 6 with slowly adapting type I (SAI) afferents 7 , 8 , 9 . These complexes, which encode spatial features such as edges and texture 1 , 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.