TY - JOUR
T1 - Epidermal Merkel cells are mechanosensory cells that tune mammalian touch receptors
AU - Maksimovic, Srdjan
AU - Nakatani, Masashi
AU - Baba, Yoshichika
AU - Nelson, Aislyn M.
AU - Marshall, Kara L.
AU - Wellnitz, Scott A.
AU - Firozi, Pervez
AU - Woo, Seung Hyun
AU - Ranade, Sanjeev
AU - Patapoutian, Ardem
AU - Lumpkin, Ellen A.
N1 - Funding Information:
Acknowledgements Thanks to R. Axel, A. MacDermott and the Lumpkin laboratory for helpful discussions and to D. Florez and R. Piskorowski for advice on whole-cell recordings. Funding was provided by NIH/NIAMS grants R01AR051219 and R21AR062307 (to E.A.L.), R01DE022358 (to A.P.) and fellowships to S.M. (5T32HL087745-05 and NIH/NINDS F32NS080544), M.N. (JSPS Research Fellowships for Young Scientists 24-7585), and A.M.N. (McNair Foundation). Microscopy and flow cytometry was performed with core support from the Columbia SDRC (P30AR044535) and Cancer Center (P30CA013696). Initial studies were performed at Baylor College of Medicine with assistance from Flow Cytometry and Genetically Engineered Mouse Shared Resources (P30CA125123).
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
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U2 - 10.1038/nature13250
DO - 10.1038/nature13250
M3 - Article
C2 - 24717432
AN - SCOPUS:84901663308
SN - 0028-0836
VL - 509
SP - 617
EP - 621
JO - Nature
JF - Nature
IS - 7502
ER -