The mechanosensory neurons of touch and their mechanisms of activation.
Journal
Nature reviews. Neuroscience
ISSN: 1471-0048
Titre abrégé: Nat Rev Neurosci
Pays: England
ID NLM: 100962781
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
accepted:
24
06
2021
pubmed:
28
7
2021
medline:
28
9
2021
entrez:
27
7
2021
Statut:
ppublish
Résumé
Our sense of touch emerges from an array of mechanosensory structures residing within the fabric of our skin. These tactile end organ structures convert innocuous forces acting on the skin into electrical signals that propagate to the CNS via the axons of low-threshold mechanoreceptors (LTMRs). Our rich capacity for tactile discrimination arises from the dissimilar intrinsic properties of the LTMR subtypes that innervate different regions of the skin and the structurally distinct end organ complexes with which they associate. These end organ structures comprise a range of non-neuronal cell types, which may themselves actively contribute to the transformation of tactile forces into neural impulses within the LTMR afferents. Although the mechanism and the site of transduction across end organs remain unclear, PIEZO2 has emerged as the principal mechanosensitive channel involved in light touch of the skin. Here we review the physiological properties of LTMR subtypes and discuss how features of their cutaneous end organ complexes shape subtype-specific tuning.
Identifiants
pubmed: 34312536
doi: 10.1038/s41583-021-00489-x
pii: 10.1038/s41583-021-00489-x
pmc: PMC8485761
mid: NIHMS1740144
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
521-537Subventions
Organisme : NICHD NIH HHS
ID : P50 HD105351
Pays : United States
Organisme : NCCIH NIH HHS
ID : R01 AT011447
Pays : United States
Organisme : NINDS NIH HHS
ID : R35 NS097344
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Informations de copyright
© 2021. Springer Nature Limited.
Références
Bai, L. et al. Genetic identification of an expansive mechanoreceptor sensitive to skin stroking. Cell 163, 1783–1795 (2015).
pubmed: 26687362
pmcid: 4890169
doi: 10.1016/j.cell.2015.11.060
Neubarth, N. L. et al. Meissner corpuscles and their spatially intermingled afferents underlie gentle touch perception. Science 368, 1–12 (2020).
doi: 10.1126/science.abb2751
Lewin, G. R. & McMahon, S. B. Physiological properties of primary sensory neurons appropriately and inappropriately innervating skin in the adult rat. J. Neurophysiol. 66, 1205–1217 (1991).
pubmed: 1761980
doi: 10.1152/jn.1991.66.4.1205
Koltzenburg, M., Stucky, C. L. & Lewin, G. R. Receptive properties of mouse sensory neurons innervating hairy skin. J. Neurophysiol. 78, 1841–1850 (1997).
pubmed: 9325353
doi: 10.1152/jn.1997.78.4.1841
Johansson, R. S., Vallbo, Å. B. & Westling, G. Thresholds of mechanosensitive afferents in the human hand as measured with von Frey hairs. Brain Res. 184, 343–351 (1980).
pubmed: 7353160
doi: 10.1016/0006-8993(80)90803-3
Cain, D. M., Khasabov, S. G. & Simone, D. A. Response properties of mechanoreceptors and nociceptors in mouse glabrous skin: an in vivo study. J. Neurophysiol. 85, 1561–1574 (2001).
pubmed: 11287480
doi: 10.1152/jn.2001.85.4.1561
Li, L. et al. The functional organization of cutaneous low-threshold mechanosensory neurons. Cell 147, 1615–1627 (2011).
pubmed: 22196735
pmcid: 3262167
doi: 10.1016/j.cell.2011.11.027
Schmidt, R. et al. Novel classes of responsive and unresponsive C nociceptors in human skin. J. Neurosci. 15, 333–341 (1995).
pubmed: 7823139
pmcid: 6578337
doi: 10.1523/JNEUROSCI.15-01-00333.1995
Bessou, P. & Perl, E. R. Response of cutaneous sensory units with unmyelinated fibers to noxious stimuli. J. Neurophysiol. 32, 1025–1043 (1969).
pubmed: 5347705
doi: 10.1152/jn.1969.32.6.1025
Perl, E. R. Myelinated afferent fibres innervating the primate skin and their response to noxious stimuli. J. Physiol. 197, 593–615 (1968).
pubmed: 4969883
pmcid: 1351750
doi: 10.1113/jphysiol.1968.sp008576
Ghitani, N. et al. Specialized mechanosensory nociceptors mediating rapid responses to hair pull. Neuron 95, 944–954 (2017).
pubmed: 28817806
pmcid: 5599122
doi: 10.1016/j.neuron.2017.07.024
Hill, R. Z. & Bautista, D. M. Getting in touch with mechanical pain mechanisms. Trends Neurosci. 43, 311–325 (2020).
pubmed: 32353335
doi: 10.1016/j.tins.2020.03.004
Arcourt, A. et al. Touch receptor-derived sensory information alleviates acute pain signaling and fine-tunes nociceptive reflex coordination. Neuron 93, 179–193 (2017).
pubmed: 27989460
doi: 10.1016/j.neuron.2016.11.027
Basbaum, A. I., Bautista, D. M., Scherrer, G. & Julius, D. Cellular and molecular mechanisms of pain. Cell 139, 267–284 (2009).
pubmed: 19837031
pmcid: 2852643
doi: 10.1016/j.cell.2009.09.028
Usoskin, D. et al. Unbiased classification of sensory neuron types by large-scale single-cell RNA sequencing. Nat. Neurosci. 18, 145–153 (2015).
pubmed: 25420068
doi: 10.1038/nn.3881
Sharma, N. et al. The emergence of transcriptional identity in somatosensory neurons. Nature 577, 392–398 (2020).
pubmed: 31915380
pmcid: 7307422
doi: 10.1038/s41586-019-1900-1
Zheng, Y. et al. Deep sequencing of somatosensory neurons reveals molecular determinants of intrinsic physiological properties. Neuron 103, 598–616 (2019).
pubmed: 31248728
pmcid: 6706313
doi: 10.1016/j.neuron.2019.05.039
Cavanaugh, D. J. et al. Distinct subsets of unmyelinated primary sensory fibers mediate behavioral responses to noxious thermal and mechanical stimuli. Proc. Natl Acad. Sci. USA 106, 9075–9080 (2009).
pubmed: 19451647
pmcid: 2683885
doi: 10.1073/pnas.0901507106
Braz, J. M., Nassar, M. A., Wood, J. N. & Basbaum, A. I. Parallel ‘pain’ pathways arise from subpopulations of primary afferent nociceptor. Neuron 47, 787–793 (2005).
pubmed: 16157274
doi: 10.1016/j.neuron.2005.08.015
Woodbury, C. J., Kullmann, F. A., McIlwrath, S. L. & Koerber, H. R. Identity of myelinated cutaneous sensory neurons projecting to nocireceptive laminae following nerve injury in adult mice. J. Comp. Neurol. 508, 500–509 (2008).
pubmed: 18335545
pmcid: 2664515
doi: 10.1002/cne.21693
Woodbury, C. J. & Koerber, H. R. Widespread projections from myelinated nociceptors throughout the substantia gelatinosa provide novel insights into neonatal hypersensitivity. J. Neurosci. 23, 601–610 (2003).
pubmed: 12533620
pmcid: 6741867
doi: 10.1523/JNEUROSCI.23-02-00601.2003
Schneider, E. R., Gracheva, E. O. & Bagriantsev, S. N. Evolutionary specialization of tactile perception in vertebrates. Physiology 31, 193–200 (2016).
pubmed: 27053733
pmcid: 5005274
doi: 10.1152/physiol.00036.2015
Gregory, J. E. An electrophysiological investigation of the receptor apparatus of the duck’s bill. J. Physiol. 229, 151–164 (1973).
pubmed: 4689962
pmcid: 1350217
doi: 10.1113/jphysiol.1973.sp010132
Catania, K. C. Structure and innervation of the sensory organs on the snout of the star-nosed mole. J. Comp. Neurol. 351, 536–548 (1995).
pubmed: 7721982
doi: 10.1002/cne.903510405
Moayedi, Y., Duenas-Bianchi, L. F. & Lumpkin, E. A. Somatosensory innervation of the oral mucosa of adult and aging mice. Sci. Rep. 8, 1–14 (2018).
doi: 10.1038/s41598-018-28195-2
Cottrell, D. F., Iggo, A. & Kitchell, R. L. Electrophysiology of the afferent innervation of the penis of the domestic ram. J. Physiol. 283, 347–367 (1978).
pubmed: 722579
pmcid: 1282782
doi: 10.1113/jphysiol.1978.sp012505
Seto, H. Studies on the Sensory Innervation (Human Sensibility) (C. C. Thomas, 1963).
Burgess, P. R., Petit, D. & Warren, R. M. Receptor types in cat hairy skin supplied by myelinated fibers. J. Neurophysiol. 31, 833–848 (1968).
pubmed: 5710537
doi: 10.1152/jn.1968.31.6.833
Paré, M., Smith, A. M. & Rice, F. L. Distribution and terminal arborizations of cutaneous mechanoreceptors in the glabrous finger pads of the monkey. J. Comp. Neurol. 445, 347–359 (2002).
pubmed: 11920712
doi: 10.1002/cne.10196
Grandry, M. Recherches sur les corpuscules de Pacini. J. anat. physiol. 6, 390–395 (1869).
Herbst, G. Die Pacinischen Körper und ihre Bedeutung. Ein Beitrag zur Kenntnis der Nervenprimitivfasern (Vandenhoeck & Ruprecht, 1848).
Brown, A. G. & Iggo, A. A quantitative study of cutaneous receptors and afferent fibres in the cat and rabbit. J. Physiol. 193, 707–733 (1967).
pubmed: 16992307
pmcid: 1365525
doi: 10.1113/jphysiol.1967.sp008390
Knibestöl, M. Stimulus — response functions of rapidly adapting mechanoreceptors in the human glabrous skin area. J. Physiol. 232, 427–452 (1973).
pubmed: 4759677
pmcid: 1350502
doi: 10.1113/jphysiol.1973.sp010279
Leem, W., Chung, J. & Willis, J. Cutaneous sensory receptors in the rat foot. J. Neurophysiol. 69, 1684–1699 (1993).
pubmed: 8509832
doi: 10.1152/jn.1993.69.5.1684
Werner, G. & Mountcastle, V. B. Neural activity in mechanoreceptive cutaneous afferents: stimulus-response relations, Weber functions, and information transmission. J. Neurophysiol. 28, 359–397 (1965).
pubmed: 14283062
doi: 10.1152/jn.1965.28.2.359
Knibestöl, M. & Vallbo, B. Intensity of sensation related to activity of slowly adapting mechanoreceptive units in the human hand. J. Physiol. 300, 251–267 (1980).
pubmed: 7381785
pmcid: 1279353
doi: 10.1113/jphysiol.1980.sp013160
Coleman, G. T., Bahramali, H., Zhang, H. Q. & Rowe, M. J. Characterization of tactile afferent fibers in the hand of the marmoset monkey. J. Neurophysiol. 85, 1793–1804 (2001).
pubmed: 11352997
doi: 10.1152/jn.2001.85.5.1793
Harrington, T. & Merzenich, M. M. Neural coding in the sense of touch: human sensations of skin indentation compared with the responses of slowly adapting mechanoreceptive afferents innervating the hairy skin of monkeys. Exp. Brain Res. 10, 251–264 (1970).
pubmed: 4985999
doi: 10.1007/BF00235049
Iggo, B. A. & Ogawa, H. Correlative physiological and morphological studies of rapidly adapting mechanoreceptors in cat’s glabrous skin. J. Physiol. 266, 275–296 (1977).
pubmed: 853451
pmcid: 1283566
doi: 10.1113/jphysiol.1977.sp011768
Vega-Bermudez, F. & Johnson, K. O. SA1 and RA receptive fields, response variability, and population responses mapped with a probe array. J. Neurophysiol. 81, 2701–2710 (1999).
pubmed: 10368390
doi: 10.1152/jn.1999.81.6.2701
Vallbo, A. B. & Johansson, R. S. The tactile sensory innervation of the glabrous skin of the human hand. in Active Touch, the Mechanism of Recognition of Objects by Manipulation (Pergamon Press, 1978).
Talbot, W. H., Darian-Smith, I., Kornhuber, H. H. & Mountcastle, V. B. The sense of flutter-vibration: comparison of the human capacity with response patterns of mechanoreceptive afferents from the monkey hand. J. Neurophysiol. 31, 301–334 (1968).
pubmed: 4972033
doi: 10.1152/jn.1968.31.2.301
Mountcastle, V. B., Talbot, W. H., Dar-Smith, I. & Kornhuber, H. H. Neural basis of the sense of flutter-vibration. Science 155, 597–600 (1967).
pubmed: 4959494
doi: 10.1126/science.155.3762.597
Vallbo, A. B. & Johansson, R. S. Properties of cutaneous mechanoreceptors in the human hand related to touch sensation. Hum. Neurobiol. 3, 3–14 (1984).
pubmed: 6330008
Roe, A., Friedman, R. & Chen, L. in Handbook of Neurochemistry and Molecular Neurobiology: Sensory Neurochemistry (eds Johnson, D. A. & LLajtha, A.) 1–16 (Springer Science+Business Media, 2007).
Knibestöl, M. & Vallbo, B. Single unit analysis of mechanoreceptor activity from the human glabrous skin. Acta Physiol. Scand. 80, 178–195 (1970).
pubmed: 5475340
doi: 10.1111/j.1748-1716.1970.tb04783.x
Johansson, R. S. & Vallbo, A. B. Tactile sensibility in the human hand: relative and absolute densities of four types of mechanoreceptive units in glabrous skin. J. Physiol. 286, 283–300 (1979).
pubmed: 439026
pmcid: 1281571
doi: 10.1113/jphysiol.1979.sp012619
Yamamoto, T. The fine structure of the palisade-type sensory endings in relation to hair follicles. J. Electron. Microsc. 15, 158–166 (1966).
Halata, Z. Sensory innervation of the hairy skin (light-and electronmicroscopic study). J. Invest. Dermatol. 101, 75S–81S (1993).
pubmed: 8326156
doi: 10.1016/0022-202X(93)90505-C
Halata, Z. & Munger, B. L. Sensory nerve endings in rhesus monkey sinus hairs. J. Comp. Neurol. 192, 645–663 (1980).
pubmed: 7419748
doi: 10.1002/cne.901920403
Iggo, A. & Muir, A. The structure and function of a slowly adapting touch corpuscle in hairy skin. J. Physiol. 1882, 763–796 (1969).
doi: 10.1113/jphysiol.1969.sp008721
Seal, R. P. et al. Injury-induced mechanical hypersensitivity requires C-low threshold mechanoreceptors. Nature 462, 651–655 (2009).
pubmed: 19915548
pmcid: 2810205
doi: 10.1038/nature08505
von Buchholtz, L. J. et al. Decoding cellular mechanisms for mechanosensory discrimination. Neuron 109, 285–298 (2021).
doi: 10.1016/j.neuron.2020.10.028
Nordin, B. Y. M. Low-threshold mechanoreceptive and nociceptive units with unmyelinated (C) fibres in the human supraorbital nerve. Physiology 426, 229–240 (1990).
doi: 10.1113/jphysiol.1990.sp018135
Iggo, A. & Kornhuber, H. H. A quantitative study of C-mechanoreceptors in hairy skin of the cat. J. Physiol. 271, 549–565 (1977).
pubmed: 926006
pmcid: 1353586
doi: 10.1113/jphysiol.1977.sp012014
Lynn, B. & Carpenter, S. E. Primary afferent units from the hairy skin of the rat hind limb. Brain Res. 238, 29–43 (1982).
pubmed: 6282398
doi: 10.1016/0006-8993(82)90768-5
Paré, M., Behets, C. & Cornu, O. Paucity of presumptive Ruffini corpuscles in the index finger pad of humans. J. Comp. Neurol. 456, 260–266 (2003).
pubmed: 12528190
doi: 10.1002/cne.10519
Gottschaldt, K. M. & Vahle-Hinz, C. Merkel cell receptors: Structure and transducer function. Science 214, 183–186 (1981).
pubmed: 7280690
doi: 10.1126/science.7280690
Rutlin, M. et al. The cellular and molecular basis of direction selectivity of Aδ-LTMRs. Cell 159, 1640–1651 (2014).
pubmed: 25525881
pmcid: 4297767
doi: 10.1016/j.cell.2014.11.038
Löken, L. S., Wessberg, J., Morrison, I., McGlone, F. & Olausson, H. Coding of pleasant touch by unmyelinated afferents in humans. Nat. Neurosci. 12, 547–548 (2009).
pubmed: 19363489
doi: 10.1038/nn.2312
Kuehn, E. D., Meltzer, S., Abraira, V. E., Ho, C. Y. & Ginty, D. D. Tiling and somatotopic alignment of mammalian low-threshold mechanoreceptors. Proc. Natl Acad. Sci. USA 116, 9168–9177 (2019).
pubmed: 30996124
pmcid: 6511030
doi: 10.1073/pnas.1901378116
Ranade, S. S. et al. Piezo2 is the major transducer of mechanical forces for touch sensation in mice. Nature 516, 121–125 (2014).
pubmed: 25471886
pmcid: 4380172
doi: 10.1038/nature13980
Woo, S. et al. Piezo2 is required for Merkel-cell mechanotransduction. Nature 509, 622–626 (2014).
pubmed: 24717433
pmcid: 4039622
doi: 10.1038/nature13251
Coste, B. et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science 330, 55–60 (2010).
pubmed: 20813920
pmcid: 3062430
doi: 10.1126/science.1193270
Ikeda, R. et al. Merkel cells transduce and encode tactile stimuli to drive aβ-afferent impulses. Cell 157, 664–675 (2014).
pubmed: 24746027
pmcid: 4003503
doi: 10.1016/j.cell.2014.02.026
Szczot, M. et al. PIEZO2 mediates injury-induced tactile pain in mice and humans. Sci. Transl. Med. 10, eaat9892 (2018).
pubmed: 30305456
pmcid: 6875774
doi: 10.1126/scitranslmed.aat9892
Chesler, A. et al. The role of PIEZO2 in human mechanosensation. N. Engl. J. Med. 375, 1355–1364 (2016).
pubmed: 27653382
pmcid: 5911918
doi: 10.1056/NEJMoa1602812
Wetzel, C. et al. A stomatin-domain protein essential for touch sensation in the mouse. Nature 445, 206–209 (2007).
pubmed: 17167420
doi: 10.1038/nature05394
Poole, K., Herget, R., Lapatsina, L., Ngo, H. D. & Lewin, G. R. Tuning Piezo ion channels to detect molecular-scale movements relevant for fine touch. Nat. Commun. 5, 1–14 (2014).
doi: 10.1038/ncomms4520
Merkel, F. Tastzellen und Tastkörperchen bei den Hausthieren und beim Menschen. Arch. Mikrosk. Anat. 11, 636–652 (1875).
doi: 10.1007/BF02933819
Ribot-Ciscar, E., Vedel, J. P. & Roll, J. P. Vibration sensitivity of slowly and rapidly adapting cutaneous mechanoreceptors in the human foot and leg. Neurosci. Lett. 104, 130–135 (1989).
pubmed: 2812525
doi: 10.1016/0304-3940(89)90342-X
Lesniak, D. R. et al. Computation identifies structural features that govern neuronal firing properties in slowly adapting touch receptors. eLife 3, e01488 (2014).
pubmed: 24448409
pmcid: 3896213
doi: 10.7554/eLife.01488
Brohawn, S. G. et al. The mechanosensitive ion channel TRAAK is localized to the mammalian node of Ranvier. eLife 8, e50403 (2019).
pubmed: 31674909
pmcid: 6824864
doi: 10.7554/eLife.50403
Kanda, H. et al. TREK-1 and TRAAK Are principal K
pubmed: 31630908
pmcid: 6895425
doi: 10.1016/j.neuron.2019.08.042
Vega-Bermudez, F. & Johnson, K. O. Surround suppression in the responses of primate SA1 and RA mechanoreceptive afferents mapped with a probe array. J. Neurophysiol. 81, 2711–2719 (1999).
pubmed: 10368391
doi: 10.1152/jn.1999.81.6.2711
Ben-Arie, N. et al. Functional conservation of atonal and Math1 in the CNS and PNS. Development 127, 1039–1048 (2000).
pubmed: 10662643
doi: 10.1242/dev.127.5.1039
Moll, R., Moll, I. & Franke, W. W. Identification of Merkel cells in human skin by specific cytokeratin antibodies: changes of cell density and distribution in fetal and adult plantar epidermis. Differentiation 28, 136–154 (1984).
pubmed: 6084624
doi: 10.1111/j.1432-0436.1984.tb00277.x
Woodbury, C. J. & Koerber, H. R. Central and peripheral anatomy of slowly adapting type I low-threshold mechanoreceptors innervating trunk skin of neonatal mice. J. Comp. Neurol. 505, 547–561 (2007).
pubmed: 17924532
doi: 10.1002/cne.21517
Kabata, Y., Orime, M., Abe, R. & Ushiki, T. The morphology, size and density of the touch dome in human hairy skin by scanning electron microscopy. Microscopy 68, 207–215 (2019).
pubmed: 30860586
doi: 10.1093/jmicro/dfz001
Zelena, J. Nerves and Mechanoreceptors (Springer, 1994).
Orime, M., Ushiki, T., Koga, D. & Ito, M. Three-dimensional morphology of touch domes in human hairy skin by correlative light and scanning electron microscopy. J. Invest. Dermatol. 133, 2108–2111 (2013).
pubmed: 23381583
doi: 10.1038/jid.2013.60
Owens, D. M. & Lumpkin, E. A. Diversification and specialization of touch receptors in skin. Cold Spring Harb. Perspect. Med. 4, a013656 (2014).
pubmed: 24890830
pmcid: 4031957
doi: 10.1101/cshperspect.a013656
Vallbo, A. B., Olausson, H., Wessberg, J. & Kakuda, N. Receptive field characteristics of tactile units with myelinated afferents in hairy skin of human subjects. J. Physiol. 483, 783–795 (1995).
pubmed: 7776258
pmcid: 1157818
doi: 10.1113/jphysiol.1995.sp020622
Pruszynski, J. A. & Johansson, R. S. Edge-orientation processing in first-order tactile neurons. Nat. Neurosci. 17, 1404–1409 (2014).
pubmed: 25174006
doi: 10.1038/nn.3804
Maksimovic, S. et al. Epidermal Merkel cells are mechanosensory cells that tune mammalian touch receptors. Nature 509, 617–621 (2014).
pubmed: 24717432
pmcid: 4097312
doi: 10.1038/nature13250
Ebara, S., Kumamoto, K., Baumann, K. I. & Halata, Z. Three-dimensional analyses of touch domes in the hairy skin of the cat paw reveal morphological substrates for complex sensory processing. Neurosci. Res. 61, 159–171 (2008).
pubmed: 18378347
doi: 10.1016/j.neures.2008.02.004
Maricich, S. M. et al. Merkel cells are essential for light-touch responses. Science 324, 1580–1582 (2009).
pubmed: 19541997
pmcid: 2743005
doi: 10.1126/science.1172890
Hitchcock, I. S., Genever, P. G. & Cahusac, P. M. B. Essential components for a glutamatergic synapse between Merkel cell and nerve terminal in rats. Neurosci. Lett. 362, 196–199 (2004).
pubmed: 15158013
doi: 10.1016/j.neulet.2004.02.071
Fagan, B. M. & Cahusac, P. M. B. Evidence for glutamate receptor mediated transmission at mechanoreceptors in the skin. Neuroreport 12, 341–347 (2001).
pubmed: 11209947
doi: 10.1097/00001756-200102120-00032
Chang, W. et al. Merkel disc is a serotonergic synapse in the epidermis for transmitting tactile signals in mammals. Proc. Natl Acad. Sci. USA 113, 491–500 (2016).
doi: 10.1073/pnas.1610176113
Chang, W. & Gu, J. G. Effects on tactile transmission by serotonin transporter inhibitors at Merkel discs of mouse whisker hair follicles. Mol. Pain https://doi.org/10.1177/1744806920938237 (2020).
doi: 10.1177/1744806920938237
pubmed: 32600103
pmcid: 7328215
Hoffman, B. U. et al. Merkel cells activate sensory neural pathways through adrenergic synapses. Neuron 100, 1401–1413 (2018).
pubmed: 30415995
pmcid: 6347413
doi: 10.1016/j.neuron.2018.10.034
Sonekatsu, M., Gu, S. L., Kanda, H. & Gu, J. G. Effects of norepinephrine and β2 receptor antagonist ICI 118,551 on whisker hair follicle mechanoreceptors dissatisfy Merkel discs being adrenergic synapses. Mol. Brain 12, 10–13 (2019).
doi: 10.1186/s13041-019-0450-7
Woo, S.-H., Lumpkin, E. A. & Patapoutian, A. Merkel cells and neurons keep in touch. Trens Cell Biol. 25, 74–81 (2015).
doi: 10.1016/j.tcb.2014.10.003
Pacini, F. Sopra un particolare genere di piccoli corpi globulosi scorpeti nel corpo umano da Filippo Pacini Aluno interna degli spedali riunti di Pistoia (Accademia Medico-fisica di Firenze, 1835).
Bell, J., Bolanowski, S. & Holmes, M. H. The structure and function of Pacinian corpuscles: a review. Prog. Neurobiol. 42, 79–128 (1994).
pubmed: 7480788
doi: 10.1016/0301-0082(94)90022-1
Zelená, J. The development of Pacinian corpuscles. J. Neurocytol. 7, 71–79 (1978).
pubmed: 632855
doi: 10.1007/BF01213461
Schwaller, F. et al. USH2A is a Meissner’s corpuscle protein necessary for normal vibration sensing in mice and humans. Nat. Neurosci. 24, 74–78 (2020).
pubmed: 33288907
doi: 10.1038/s41593-020-00751-y
Wende, H. et al. The transcription factor c-Maf controls touch receptor development and function. Science 335, 1373–1376 (2012).
pubmed: 22345400
doi: 10.1126/science.1214314
Alvarez-Buylla, R. & de Arellano, J. Local responses in Pacinian corpuscles. Am. J. Physiol. 172, 237–244 (1953).
pubmed: 13030743
doi: 10.1152/ajplegacy.1952.172.1.237
Brisben, A. J., Hsiao, S. S. & Johnson, K. O. Detection of vibration transmitted through an object grasped in the hand. J. Neurophysiol. 81, 1548–1558 (1999).
pubmed: 10200190
doi: 10.1152/jn.1999.81.4.1548
Mountcastle, V. B., LaMotte, R. H. & Carli, G. Detection thresholds for stimuli in humans and monkeys: comparison with threshold events in mechanoreceptive afferent nerve fibers innervating the monkey hand. J. Neurophysiol. 35, 122–136 (1972).
pubmed: 4621505
doi: 10.1152/jn.1972.35.1.122
Johnson, K. O. The roles and functions of cutaneous mechanoreceptors. Curr. Opin. Neurobiol. 11, 455–461 (2001).
pubmed: 11502392
doi: 10.1016/S0959-4388(00)00234-8
Luo, W., Enomoto, H., Rice, F. L., Milbrandt, J. & Ginty, D. D. Molecular identification of rapidly adapting mechanoreceptors and their developmental dependence on ret signaling. Neuron 64, 841–856 (2009).
pubmed: 20064391
pmcid: 2813518
doi: 10.1016/j.neuron.2009.11.003
Pease, D. C. & Quilliam, T. A. Electron microscopy of the Pacinian corpuscle. J. Biophys. Biochem. Cytol. 3, 331–342 (1957).
pubmed: 13438918
pmcid: 2224036
doi: 10.1083/jcb.3.3.331
Vega, J. A. et al. The inner-core, outer-core and capsule cells of the human Pacinian corpuscles: an immunohistochemical study. Eur. J. Morphol. 32, 11–18 (1994).
pubmed: 7522027
Spencer, P. S. & Schaumburg, H. H. An ultrastructural study of the inner core of the Pacinian corpuscle. J. Neurocytol. 2, 217–235 (1973).
pubmed: 4775768
doi: 10.1007/BF01474721
Vega, J. A., García-Suárez, O., Montaño, J. A., Pardo, B. & Cobo, J. M. The Meissner and Pacinian sensory corpuscles revisited new data from the last decade. Microsc. Res. Tech. 72, 299–309 (2009).
pubmed: 19012318
doi: 10.1002/jemt.20651
García-Piqueras, J. et al. Endoneurial-CD34 positive cells define an intermediate layer in human digital Pacinian corpuscles. Ann. Anat. 211, 55–60 (2017).
pubmed: 28163202
doi: 10.1016/j.aanat.2017.01.006
Loewenstein, W. On the ‘specificity’ of a sensory receptor. J. Neurophysiol. 24, 150–158 (1961).
pubmed: 13763137
doi: 10.1152/jn.1961.24.2.150
Loewenstein, W. Excitation inactivation a receptor membrane. Ann. N. Y. Acad. Sci. 94, 510–534 (1961).
pubmed: 13763135
doi: 10.1111/j.1749-6632.1961.tb35556.x
Loewenstein, W. & Mendelson, M. Components of receptor adaptation in a Pacinian corpuscle. J. Physiol. 177, 377–397 (1965).
pubmed: 14321486
pmcid: 1357253
doi: 10.1113/jphysiol.1965.sp007598
Nikolaev, Y. A. et al. Lamellar cells in Pacinian and Meissner corpuscles are touch sensors. Sci. Adv. 6, eabe6393 (2020).
pubmed: 33328243
pmcid: 7744075
doi: 10.1126/sciadv.abe6393
García-Mesa, Y. et al. Merkel cells and Meissner’s corpuscles in human digital skin display Piezo2 immunoreactivity. J. Anat. 231, 978–989 (2017).
pubmed: 28905996
pmcid: 5696134
doi: 10.1111/joa.12688
Quindlen, J. C., Stolarski, H. K., Johnson, M. D. & Barocas, V. H. A multiphysics model of the Pacinian corpuscle. Integr. Biol. 8, 1111–1125 (2016).
doi: 10.1039/C6IB00157B
Pawson, L. et al. GABAergic/glutamatergic-glial/neuronal interaction contributes to rapid adaptation in Pacinian corpuscles. J. Neurosci. 29, 2695–2705 (2009).
pubmed: 19261864
pmcid: 2727419
doi: 10.1523/JNEUROSCI.5974-08.2009
Wagner, R. & Meissner, G. Uber das Vorhandensein bisher unbekannter eigenthumlicher Tastkorperchen (corpuscula tactus) in den Gefuhlswarzchen der menschlichen Haut und uber die Endausbreitung sensitiver Nerven. Nachrichten von der Georg-August-Universität u d Königl Ges d Wissench zu Göttingen. 17–30 (1852).
LaMotte, R. H. & Whitehouse, J. Tactile detection of a dot on a smooth surface: Peripheral neural events. J. Neurophysiol. 56, 1109–1128 (1986).
pubmed: 3097273
doi: 10.1152/jn.1986.56.4.1109
Lindblom, U. Properties of touch receptors in distal glabrous skin of the monkey. J. Neurophysiol. 28, 966–985 (1965).
pubmed: 4956282
doi: 10.1152/jn.1965.28.5.966
Srinivasan, M. A., Whitehouse, J. M. & LaMotte, R. H. Tactile detection of slip: surface microgeometry and peripheral neural codes. J. Neurophysiol. 63, 1323–1332 (1990).
pubmed: 2358880
doi: 10.1152/jn.1990.63.6.1323
Freeman, A. W. & Johnson, K. O. A model accounting for effects of vibratory amplitude on responses of cutaneous mechanoreceptors in macaque monkey. J. Physiol. 323, 43–64 (1982).
pubmed: 7097579
pmcid: 1250344
doi: 10.1113/jphysiol.1982.sp014060
Johnson, K. O., Yoshioka, T. & Vega Bermudez, F. Tactile functions of mechanoreceptive afferents innervating the hand. J. Clin. Neurophysiol. 17, 539–558 (2000).
pubmed: 11151974
doi: 10.1097/00004691-200011000-00002
Idé, C. Development of Meissner corpuscle of mouse toe pad. Anat. Rec. 188, 49–67 (1977).
pubmed: 869232
doi: 10.1002/ar.1091880107
Hashimoto, K. Fine structure of the Meissner corpuscle of human palmar skin. J. Invest. Dermatol. 60, 20–28 (1973).
pubmed: 4684157
doi: 10.1111/1523-1747.ep13069657
Takahashi-Iwanaga, H. The three-dimensional microanatomy of Meissner corpuscles in monkey palmar skin. J. Neurocytol. 32, 363–371 (2003).
pubmed: 14724379
doi: 10.1023/B:NEUR.0000011330.57530.2f
Cuana, N. & Ross, L. L. The fine structure of Meissner’s touch corpuscles of human fingers. J. Biophys. Biochem. Cytol. 8, 467–482 (1960).
doi: 10.1083/jcb.8.2.467
Idé, C. The fine structure of the digital corpuscle of the mouse toe pad, with special reference to nerve fibers. Am. J. Anat. 147, 329–355 (1976).
pubmed: 983972
doi: 10.1002/aja.1001470307
Walcher, J. et al. Specialized mechanoreceptor systems in rodent glabrous skin. J. Physiol. 596, 4995–5016 (2018).
pubmed: 30132906
pmcid: 6187043
doi: 10.1113/JP276608
Heidenreich, M. et al. KCNQ4 K
pubmed: 22101641
doi: 10.1038/nn.2985
Chiang, L. Y. et al. Laminin-332 coordinates mechanotransduction and growth cone bifurcation in sensory neurons. Nat. Neurosci. 14, 993–1000 (2011).
pubmed: 21725315
doi: 10.1038/nn.2873
Hu, J., Chiang, L. Y., Koch, M. & Lewin, G. R. Evidence for a protein tether involved in somatic touch. EMBO J. 29, 855–867 (2010).
pubmed: 20075867
pmcid: 2810375
doi: 10.1038/emboj.2009.398
Wu, H., Williams, J. & Nathans, J. Morphologic diversity of cutaneous sensory afferents revealed by genetically directed sparse labeling. Elife 1, e00181 (2012).
pubmed: 23256042
pmcid: 3524796
doi: 10.7554/eLife.00181
Bourane, S. et al. Low-threshold mechanoreceptor subtypes selectively express MafA and are specified by Ret signaling. Neuron 64, 857–870 (2009).
pubmed: 20064392
doi: 10.1016/j.neuron.2009.12.004
Iggo, A. Cutaneous mechanoreceptors with afferent C fibres. J. Physiol. 152, 337–353 (1960).
pubmed: 13852622
pmcid: 1363319
doi: 10.1113/jphysiol.1960.sp006491
François, A. et al. The low-threshold calcium channel Cav3.2 determines low-threshold mechanoreceptor function. Cell Rep. 10, 370–382 (2015).
pubmed: 25600872
doi: 10.1016/j.celrep.2014.12.042
Wang, R. & Lewin, G. R. The Cav3.2 T-type calcium channel regulates temporal coding in mouse mechanoreceptors. J. Physiol. 589, 2229–2243 (2011).
pubmed: 21486775
pmcid: 3098700
doi: 10.1113/jphysiol.2010.203463
Zotterman, Y. Touch, pain and tickling: an electro-physiological investigation on cutaneous sensory nerves. J. Physiol. 95, 1–28 (1939).
pubmed: 16995068
pmcid: 1393960
doi: 10.1113/jphysiol.1939.sp003707
Vallbo, Å., Olausson, H., Wessberg, J. & Norrsell, U. A system of unmyelinated afferents for innocuous mechanoreception in the human skin. Brain Res. 628, 301–304 (1993).
pubmed: 8313159
doi: 10.1016/0006-8993(93)90968-S
Abraira, V. et al. The cellular and synaptic architecture of the mechanosensory dorsal horn. Cell 168, 295–310 (2017).
pubmed: 28041852
pmcid: 5236062
doi: 10.1016/j.cell.2016.12.010
Hashimoto, K. Fine structure of perifollicular nerve endings in human hair. J. Invest. Dermatol. 59, 432–441 (1972).
pubmed: 4643882
doi: 10.1111/1523-1747.ep12627604
Li, L. & Ginty, D. D. The structure and organization of lanceolate mechanosensory complexes at mouse hair follicles. eLife 3, e01901 (2014).
pubmed: 24569481
pmcid: 3930909
doi: 10.7554/eLife.01901
Kaidoh, T. & Inoué, T. Intercellular junctions between palisade nerve endings and outer root sheath cells of rat vellus hairs. J. Comp. Neurol. 420, 419–427 (2000).
pubmed: 10805917
doi: 10.1002/(SICI)1096-9861(20000515)420:4<419::AID-CNE1>3.0.CO;2-3
Kaidoh, T. & Inoué, T. N-cadherin expression in palisade nerve endings of rat vellus hairs. J. Comp. Neurol. 506, 525–534 (2008).
pubmed: 18067145
doi: 10.1002/cne.21550
Takahashi-Iwanaga, H. Three-dimensional microanatomy of longitudinal lanceolate endings in rat vibrissae. J. Comp. Neurol. 426, 259–269 (2000).
pubmed: 10982467
doi: 10.1002/1096-9861(20001016)426:2<259::AID-CNE7>3.0.CO;2-N
Fünfschilling, U. et al. TrkC kinase expression in distinct subsets of cutaneous trigeminal innervation and nonneuronal cells. J. Comp. Neurol. 480, 392–414 (2004).
pubmed: 15558783
pmcid: 2710130
doi: 10.1002/cne.20359
Chambers, M. R., Andres, K. H., Duering, M. & Iggo, A. The structure and function of the slowly adapting type II mechanoreceptor in hairy skin. Q. J. Exp. Physiol. Cogn. Med. Sci. 57, 417–445 (1972).
pubmed: 4484588
Wellnitz, S. A., Lesniak, D. R., Gerling, G. J. & Lumpkin, E. A. The regularity of sustained firing reveals two populations of slowly adapting touch receptors in mouse hairy skin. J. Neurophysiol. 103, 3378–3388 (2010).
pubmed: 20393068
pmcid: 2888253
doi: 10.1152/jn.00810.2009
Chambers, M. R. & Iggo, A. Slowly-adapting cutaneous mechanoreceptors. J. Physiol. 192, 26P–27P (1967).
pubmed: 6050148
Merzenich, M. M. & Harrington, T. The sense of flutter-vibration evoked by stimulation of the hairy skin of primates: comparison of human sensory capacity with the responses of mechanoreceptive afferents innervating the hairy skin of monkeys. Exp. Brain Res. 9, 236–260 (1969).
pubmed: 4984464
doi: 10.1007/BF00234457
Edin, B. B. Quantitative analysis of static strain sensitivity in human mechanoreceptors from hairy skin. J. Neurophysiol. 67, 1105–1113 (1992).
pubmed: 1597700
doi: 10.1152/jn.1992.67.5.1105
Fleming, M. S. & Luo, W. The anatomy, function, and development of mammalian Aβ low-threshold mechanoreceptors. Front. Biol. 8, 408–420 (2013).
doi: 10.1007/s11515-013-1271-1
Halata, Z., Rettig, T. & Schulze, W. The ultrastructure of sensory nerve endings in the human knee joint capsule. Anat. Embryol. 172, 265–275 (1985).
doi: 10.1007/BF00318974
Rice, F. L. & Rasmusson, D. D. Innervation of the digit on the forepaw of the raccoon. J. Comp. Neurol. 417, 467–490 (2000).
pubmed: 10701867
doi: 10.1002/(SICI)1096-9861(20000221)417:4<467::AID-CNE6>3.0.CO;2-Q
Byers, M. R. Sensory innervation of periodontal ligament of rat molars consists of unencapsulated Ruffini-like mechanoreceptors and free nerve endings. J. Comp. Neurol. 231, 500–518 (1985).
pubmed: 3968252
doi: 10.1002/cne.902310408
Rasmusson, D. D. & Turnbull, B. G. Sensory innervation of the raccoon forepaw: 2. Response properties and classification of slowly adapting fibers. Somatosens. Mot. Res. 4, 63–75 (1986).
doi: 10.3109/07367228609144598
Li, C. L. et al. Somatosensory neuron types identified by high-coverage single-cell RNA-sequencing and functional heterogeneity. Cell Res. 26, 83–102 (2016).
pubmed: 26691752
doi: 10.1038/cr.2015.149
Nguyen, M. Q., Wu, Y., Bonilla, L. S., von Buchholtz, L. J. & Ryba, N. J. P. Diversity amongst trigeminal neurons revealed by high throughput single cell sequencing. PLoS ONE 12, e0185543 (2017).
pubmed: 28957441
pmcid: 5619795
doi: 10.1371/journal.pone.0185543
Abdo, H. et al. Specialized cutaneous Schwann cells initiate pain sensation. Science 365, 695–699 (2019).
pubmed: 31416963
doi: 10.1126/science.aax6452
Moehring, F. et al. Keratinocytes mediate innocuous and noxious touch via ATP-P2X4 signaling. eLife 7, e31684 (2018).
pubmed: 29336303
pmcid: 5777822
doi: 10.7554/eLife.31684
Winkelmann, R. K. The mucocutaneous end-organ: the primary organized sensory ending in human skin. AMA Arch. Derm. 76, 225–235 (1957).
pubmed: 13443512
doi: 10.1001/archderm.1957.01550200069015
Yamada, K. On the sensory nerve terminations in clitoris in human adult. Tohoku J. Exp. Med. 54, 163–174 (1951).
pubmed: 14884179
doi: 10.1620/tjem.54.163
Gairns, F. W. The sensory nerve endings of the human palate. Q. J. Exp. Physiol. Cogn. Med. Sci. 40, 40–48 (1955).
pubmed: 14371989
Cathcart, E. P., Gairns, F. W. & Garven, H. S. D. The innervation of the human quiescent nipple, with notes on pigmentation, erection, and hyperneury. Trans. R. Soc. Edinb. 61, 699–717 (1949).
doi: 10.1017/S0080456800019104
Ohmori, D. Über die Entwicklung der Innervation der Genitalapparate als peripheren Aufnahmeapparat der genitalen Reflexe. Z. Anat. Entwicklungsgesch. 70, 347–410 (1924).
doi: 10.1007/BF02117201
Krause, W. Uber die Nervenendigung in den Geschlechtsorganen. Z. Nat. Medizin. XXVII, 86–88 (1866).
McNeilly, A. S. Physiology of lactation. J. Biosoc. Sci. 9, 5–21 (1977).
doi: 10.1017/S0021932000023804
Katz, D. The world of touch. Translated by Lester E. Krueger. (Routledge, 2016).
Rieke, F., Bodnar, D. A. & Bialek, W. Naturalistic stimuli increase the rate and efficiency of information transmission by primary auditory afferents. Proc. R. Soc. B Biol. Sci. 262, 259–265 (1995).
doi: 10.1098/rspb.1995.0204
Lewicki, M. S. Efficient coding of natural sounds. Nat. Neurosci. 5, 356–363 (2002).
pubmed: 11896400
doi: 10.1038/nn831
Leiser, S. C. & Moxon, K. A. Responses of trigeminal ganglion neurons during natural whisking behaviors in the awake rat. Neuron 53, 117–133 (2007).
pubmed: 17196535
doi: 10.1016/j.neuron.2006.10.036
Blake, D. T., Hsiao, S. S. & Johnson, K. O. Neural coding mechanisms in tactile pattern recognition: The relative contributions of slowly and rapidly adapting mechanoreceptors to perceived roughness. J. Neurosci. 17, 7480–7489 (1997).
pubmed: 9295394
pmcid: 6573449
doi: 10.1523/JNEUROSCI.17-19-07480.1997
Macefield, V. G., Häger-Ross, C. & Johansson, R. S. Control of grip force during restraint of an object held between finger and thumb: responses of cutaneous afferents from the digits. Exp. Brain Res. 108, 155–171 (1996).
pubmed: 8721164
Severson, K. S. et al. Active touch and self-motion encoding by Merkel cell-associated afferents. Neuron 94, 666–676 (2017).
pubmed: 28434802
pmcid: 5528144
doi: 10.1016/j.neuron.2017.03.045
Hulliger, M., Nordh, E., Thelin, A. E. & Vallbo, A. B. The responses of afferent fibres from the glabrous skin of the hand during voluntary finger movements in man. J. Physiol. 291, 233–249 (1979).
pubmed: 480210
pmcid: 1280897
doi: 10.1113/jphysiol.1979.sp012809
Olson, W. et al. Sparse genetic tracing reveals regionally specific functional organization of mammalian nociceptors. eLife 6, e29507 (2017).
pubmed: 29022879
pmcid: 5648527
doi: 10.7554/eLife.29507
Zylka, M. J., Rice, F. L. & Anderson, D. J. Topographically distinct epidermal nociceptive circuits revealed by axonal tracers targeted to Mrgprd. Neuron 45, 17–25 (2005).
pubmed: 15629699
doi: 10.1016/j.neuron.2004.12.015
Paré, M., Elde, R., Mazurkiewicz, J. E., Smith, A. M. & Rice, F. L. The Meissner corpuscle revised: a multiafferented mechanoreceptor with nociceptor immunochemical properties. J. Neurosci. 21, 7236–7246 (2001).
pubmed: 11549734
pmcid: 6763005
doi: 10.1523/JNEUROSCI.21-18-07236.2001