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The mechanosensory neurons of touch and their mechanisms of activation

Abstract

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.

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Fig. 1: The mechanoreceptors of mammalian glabrous skin.
Fig. 2: The mechanoreceptors of mammalian hairy skin.
Fig. 3: The Merkel cell–neurite complex.
Fig. 4: The structure and function of the Pacinian corpuscle.
Fig. 5: The structure and function of the Meissner corpuscle.
Fig. 6: Ultrastructural features of lanceolate and circumferential endings.

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References

  1. Bai, L. et al. Genetic identification of an expansive mechanoreceptor sensitive to skin stroking. Cell 163, 1783–1795 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Neubarth, N. L. et al. Meissner corpuscles and their spatially intermingled afferents underlie gentle touch perception. Science 368, 1–12 (2020).

    Article  CAS  Google Scholar 

  3. 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).

    Article  CAS  PubMed  Google Scholar 

  4. Koltzenburg, M., Stucky, C. L. & Lewin, G. R. Receptive properties of mouse sensory neurons innervating hairy skin. J. Neurophysiol. 78, 1841–1850 (1997).

    Article  CAS  PubMed  Google Scholar 

  5. 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).

    Article  CAS  PubMed  Google Scholar 

  6. 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).

    Article  CAS  PubMed  Google Scholar 

  7. Li, L. et al. The functional organization of cutaneous low-threshold mechanosensory neurons. Cell 147, 1615–1627 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Schmidt, R. et al. Novel classes of responsive and unresponsive C nociceptors in human skin. J. Neurosci. 15, 333–341 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bessou, P. & Perl, E. R. Response of cutaneous sensory units with unmyelinated fibers to noxious stimuli. J. Neurophysiol. 32, 1025–1043 (1969).

    Article  CAS  PubMed  Google Scholar 

  10. Perl, E. R. Myelinated afferent fibres innervating the primate skin and their response to noxious stimuli. J. Physiol. 197, 593–615 (1968).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ghitani, N. et al. Specialized mechanosensory nociceptors mediating rapid responses to hair pull. Neuron 95, 944–954 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hill, R. Z. & Bautista, D. M. Getting in touch with mechanical pain mechanisms. Trends Neurosci. 43, 311–325 (2020).

    Article  CAS  PubMed  Google Scholar 

  13. Arcourt, A. et al. Touch receptor-derived sensory information alleviates acute pain signaling and fine-tunes nociceptive reflex coordination. Neuron 93, 179–193 (2017).

    Article  CAS  PubMed  Google Scholar 

  14. Basbaum, A. I., Bautista, D. M., Scherrer, G. & Julius, D. Cellular and molecular mechanisms of pain. Cell 139, 267–284 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Usoskin, D. et al. Unbiased classification of sensory neuron types by large-scale single-cell RNA sequencing. Nat. Neurosci. 18, 145–153 (2015).

    Article  CAS  PubMed  Google Scholar 

  16. Sharma, N. et al. The emergence of transcriptional identity in somatosensory neurons. Nature 577, 392–398 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zheng, Y. et al. Deep sequencing of somatosensory neurons reveals molecular determinants of intrinsic physiological properties. Neuron 103, 598–616 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. 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).

    Article  CAS  PubMed  Google Scholar 

  20. 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).

    Article  PubMed  PubMed Central  Google Scholar 

  21. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Schneider, E. R., Gracheva, E. O. & Bagriantsev, S. N. Evolutionary specialization of tactile perception in vertebrates. Physiology 31, 193–200 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Gregory, J. E. An electrophysiological investigation of the receptor apparatus of the duck’s bill. J. Physiol. 229, 151–164 (1973).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. 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).

    Article  CAS  PubMed  Google Scholar 

  25. 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).

    Article  CAS  Google Scholar 

  26. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Seto, H. Studies on the Sensory Innervation (Human Sensibility) (C. C. Thomas, 1963).

  28. Burgess, P. R., Petit, D. & Warren, R. M. Receptor types in cat hairy skin supplied by myelinated fibers. J. Neurophysiol. 31, 833–848 (1968).

    Article  CAS  PubMed  Google Scholar 

  29. 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).

    Article  PubMed  Google Scholar 

  30. Grandry, M. Recherches sur les corpuscules de Pacini. J. anat. physiol. 6, 390–395 (1869).

    Google Scholar 

  31. Herbst, G. Die Pacinischen Körper und ihre Bedeutung. Ein Beitrag zur Kenntnis der Nervenprimitivfasern (Vandenhoeck & Ruprecht, 1848).

  32. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Knibestöl, M. Stimulus — response functions of rapidly adapting mechanoreceptors in the human glabrous skin area. J. Physiol. 232, 427–452 (1973).

    Article  PubMed  PubMed Central  Google Scholar 

  34. Leem, W., Chung, J. & Willis, J. Cutaneous sensory receptors in the rat foot. J. Neurophysiol. 69, 1684–1699 (1993).

    Article  CAS  PubMed  Google Scholar 

  35. 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).

    Article  CAS  PubMed  Google Scholar 

  36. 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).

    Article  PubMed  PubMed Central  Google Scholar 

  37. 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).

    Article  CAS  PubMed  Google Scholar 

  38. 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).

    Article  CAS  PubMed  Google Scholar 

  39. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. 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).

    Article  CAS  PubMed  Google Scholar 

  41. 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).

  42. 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).

    Article  CAS  PubMed  Google Scholar 

  43. 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).

    Article  CAS  PubMed  Google Scholar 

  44. Vallbo, A. B. & Johansson, R. S. Properties of cutaneous mechanoreceptors in the human hand related to touch sensation. Hum. Neurobiol. 3, 3–14 (1984).

    CAS  PubMed  Google Scholar 

  45. 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).

  46. Knibestöl, M. & Vallbo, B. Single unit analysis of mechanoreceptor activity from the human glabrous skin. Acta Physiol. Scand. 80, 178–195 (1970).

    Article  PubMed  Google Scholar 

  47. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Yamamoto, T. The fine structure of the palisade-type sensory endings in relation to hair follicles. J. Electron. Microsc. 15, 158–166 (1966).

    CAS  Google Scholar 

  49. Halata, Z. Sensory innervation of the hairy skin (light-and electronmicroscopic study). J. Invest. Dermatol. 101, 75S–81S (1993).

    Article  CAS  PubMed  Google Scholar 

  50. Halata, Z. & Munger, B. L. Sensory nerve endings in rhesus monkey sinus hairs. J. Comp. Neurol. 192, 645–663 (1980).

    Article  CAS  PubMed  Google Scholar 

  51. Iggo, A. & Muir, A. The structure and function of a slowly adapting touch corpuscle in hairy skin. J. Physiol. 1882, 763–796 (1969).

    Article  Google Scholar 

  52. Seal, R. P. et al. Injury-induced mechanical hypersensitivity requires C-low threshold mechanoreceptors. Nature 462, 651–655 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. von Buchholtz, L. J. et al. Decoding cellular mechanisms for mechanosensory discrimination. Neuron 109, 285–298 (2021).

    Article  CAS  Google Scholar 

  54. Nordin, B. Y. M. Low-threshold mechanoreceptive and nociceptive units with unmyelinated (C) fibres in the human supraorbital nerve. Physiology 426, 229–240 (1990).

    Article  CAS  Google Scholar 

  55. Iggo, A. & Kornhuber, H. H. A quantitative study of C-mechanoreceptors in hairy skin of the cat. J. Physiol. 271, 549–565 (1977).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Lynn, B. & Carpenter, S. E. Primary afferent units from the hairy skin of the rat hind limb. Brain Res. 238, 29–43 (1982).

    Article  CAS  PubMed  Google Scholar 

  57. 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).

    Article  PubMed  Google Scholar 

  58. Gottschaldt, K. M. & Vahle-Hinz, C. Merkel cell receptors: Structure and transducer function. Science 214, 183–186 (1981).

    Article  CAS  PubMed  Google Scholar 

  59. Rutlin, M. et al. The cellular and molecular basis of direction selectivity of Aδ-LTMRs. Cell 159, 1640–1651 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. 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).

    Article  PubMed  CAS  Google Scholar 

  61. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Ranade, S. S. et al. Piezo2 is the major transducer of mechanical forces for touch sensation in mice. Nature 516, 121–125 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Woo, S. et al. Piezo2 is required for Merkel-cell mechanotransduction. Nature 509, 622–626 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Coste, B. et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science 330, 55–60 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Ikeda, R. et al. Merkel cells transduce and encode tactile stimuli to drive aβ-afferent impulses. Cell 157, 664–675 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Szczot, M. et al. PIEZO2 mediates injury-induced tactile pain in mice and humans. Sci. Transl. Med. 10, eaat9892 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Chesler, A. et al. The role of PIEZO2 in human mechanosensation. N. Engl. J. Med. 375, 1355–1364 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Wetzel, C. et al. A stomatin-domain protein essential for touch sensation in the mouse. Nature 445, 206–209 (2007).

    Article  CAS  PubMed  Google Scholar 

  69. 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).

    Article  CAS  Google Scholar 

  70. Merkel, F. Tastzellen und Tastkörperchen bei den Hausthieren und beim Menschen. Arch. Mikrosk. Anat. 11, 636–652 (1875).

    Article  Google Scholar 

  71. 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).

    Article  CAS  PubMed  Google Scholar 

  72. Lesniak, D. R. et al. Computation identifies structural features that govern neuronal firing properties in slowly adapting touch receptors. eLife 3, e01488 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  73. Brohawn, S. G. et al. The mechanosensitive ion channel TRAAK is localized to the mammalian node of Ranvier. eLife 8, e50403 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  74. Kanda, H. et al. TREK-1 and TRAAK Are principal K+ channels at the nodes of Ranvier for rapid action potential conduction on mammalian myelinated afferent nerves. Neuron 104, 960–971 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. 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).

    Article  CAS  PubMed  Google Scholar 

  76. Ben-Arie, N. et al. Functional conservation of atonal and Math1 in the CNS and PNS. Development 127, 1039–1048 (2000).

    Article  CAS  PubMed  Google Scholar 

  77. 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).

    Article  CAS  PubMed  Google Scholar 

  78. 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).

    Article  PubMed  Google Scholar 

  79. 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).

    Article  CAS  PubMed  Google Scholar 

  80. Zelena, J. Nerves and Mechanoreceptors (Springer, 1994).

  81. 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).

    Article  CAS  PubMed  Google Scholar 

  82. Owens, D. M. & Lumpkin, E. A. Diversification and specialization of touch receptors in skin. Cold Spring Harb. Perspect. Med. 4, a013656 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Pruszynski, J. A. & Johansson, R. S. Edge-orientation processing in first-order tactile neurons. Nat. Neurosci. 17, 1404–1409 (2014).

    Article  CAS  PubMed  Google Scholar 

  85. Maksimovic, S. et al. Epidermal Merkel cells are mechanosensory cells that tune mammalian touch receptors. Nature 509, 617–621 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. 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).

    Article  PubMed  Google Scholar 

  87. Maricich, S. M. et al. Merkel cells are essential for light-touch responses. Science 324, 1580–1582 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. 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).

    Article  CAS  PubMed  Google Scholar 

  89. Fagan, B. M. & Cahusac, P. M. B. Evidence for glutamate receptor mediated transmission at mechanoreceptors in the skin. Neuroreport 12, 341–347 (2001).

    Article  CAS  PubMed  Google Scholar 

  90. 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).

    Article  CAS  Google Scholar 

  91. 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).

    Article  PubMed  PubMed Central  Google Scholar 

  92. Hoffman, B. U. et al. Merkel cells activate sensory neural pathways through adrenergic synapses. Neuron 100, 1401–1413 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. 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).

    Article  Google Scholar 

  94. Woo, S.-H., Lumpkin, E. A. & Patapoutian, A. Merkel cells and neurons keep in touch. Trens Cell Biol. 25, 74–81 (2015).

    Article  Google Scholar 

  95. 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).

  96. Bell, J., Bolanowski, S. & Holmes, M. H. The structure and function of Pacinian corpuscles: a review. Prog. Neurobiol. 42, 79–128 (1994).

    Article  CAS  PubMed  Google Scholar 

  97. Zelená, J. The development of Pacinian corpuscles. J. Neurocytol. 7, 71–79 (1978).

    Article  PubMed  Google Scholar 

  98. 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).

    Article  PubMed  CAS  Google Scholar 

  99. Wende, H. et al. The transcription factor c-Maf controls touch receptor development and function. Science 335, 1373–1376 (2012).

    Article  CAS  PubMed  Google Scholar 

  100. Alvarez-Buylla, R. & de Arellano, J. Local responses in Pacinian corpuscles. Am. J. Physiol. 172, 237–244 (1953).

    Article  CAS  PubMed  Google Scholar 

  101. 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).

    Article  CAS  PubMed  Google Scholar 

  102. 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).

    Article  CAS  PubMed  Google Scholar 

  103. Johnson, K. O. The roles and functions of cutaneous mechanoreceptors. Curr. Opin. Neurobiol. 11, 455–461 (2001).

    Article  CAS  PubMed  Google Scholar 

  104. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Pease, D. C. & Quilliam, T. A. Electron microscopy of the Pacinian corpuscle. J. Biophys. Biochem. Cytol. 3, 331–342 (1957).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. 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).

    CAS  PubMed  Google Scholar 

  107. Spencer, P. S. & Schaumburg, H. H. An ultrastructural study of the inner core of the Pacinian corpuscle. J. Neurocytol. 2, 217–235 (1973).

    Article  CAS  PubMed  Google Scholar 

  108. 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).

    Article  PubMed  Google Scholar 

  109. García-Piqueras, J. et al. Endoneurial-CD34 positive cells define an intermediate layer in human digital Pacinian corpuscles. Ann. Anat. 211, 55–60 (2017).

    Article  PubMed  Google Scholar 

  110. Loewenstein, W. On the ‘specificity’ of a sensory receptor. J. Neurophysiol. 24, 150–158 (1961).

    Article  CAS  PubMed  Google Scholar 

  111. Loewenstein, W. Excitation inactivation a receptor membrane. Ann. N. Y. Acad. Sci. 94, 510–534 (1961).

    Article  CAS  PubMed  Google Scholar 

  112. Loewenstein, W. & Mendelson, M. Components of receptor adaptation in a Pacinian corpuscle. J. Physiol. 177, 377–397 (1965).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Nikolaev, Y. A. et al. Lamellar cells in Pacinian and Meissner corpuscles are touch sensors. Sci. Adv. 6, eabe6393 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. García-Mesa, Y. et al. Merkel cells and Meissner’s corpuscles in human digital skin display Piezo2 immunoreactivity. J. Anat. 231, 978–989 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. 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).

    Article  CAS  Google Scholar 

  116. Pawson, L. et al. GABAergic/glutamatergic-glial/neuronal interaction contributes to rapid adaptation in Pacinian corpuscles. J. Neurosci. 29, 2695–2705 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. 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).

  118. LaMotte, R. H. & Whitehouse, J. Tactile detection of a dot on a smooth surface: Peripheral neural events. J. Neurophysiol. 56, 1109–1128 (1986).

    Article  CAS  PubMed  Google Scholar 

  119. Lindblom, U. Properties of touch receptors in distal glabrous skin of the monkey. J. Neurophysiol. 28, 966–985 (1965).

    Article  CAS  PubMed  Google Scholar 

  120. 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).

    Article  CAS  PubMed  Google Scholar 

  121. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Johnson, K. O., Yoshioka, T. & Vega Bermudez, F. Tactile functions of mechanoreceptive afferents innervating the hand. J. Clin. Neurophysiol. 17, 539–558 (2000).

    Article  CAS  PubMed  Google Scholar 

  123. Idé, C. Development of Meissner corpuscle of mouse toe pad. Anat. Rec. 188, 49–67 (1977).

    Article  PubMed  Google Scholar 

  124. Hashimoto, K. Fine structure of the Meissner corpuscle of human palmar skin. J. Invest. Dermatol. 60, 20–28 (1973).

    Article  CAS  PubMed  Google Scholar 

  125. Takahashi-Iwanaga, H. The three-dimensional microanatomy of Meissner corpuscles in monkey palmar skin. J. Neurocytol. 32, 363–371 (2003).

    Article  PubMed  Google Scholar 

  126. Cuana, N. & Ross, L. L. The fine structure of Meissner’s touch corpuscles of human fingers. J. Biophys. Biochem. Cytol. 8, 467–482 (1960).

    Article  Google Scholar 

  127. 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).

    Article  PubMed  Google Scholar 

  128. Walcher, J. et al. Specialized mechanoreceptor systems in rodent glabrous skin. J. Physiol. 596, 4995–5016 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Heidenreich, M. et al. KCNQ4 K+ channels tune mechanoreceptors for normal touch sensation in mouse and man. Nat. Neurosci. 15, 138–145 (2011).

    Article  PubMed  CAS  Google Scholar 

  130. Chiang, L. Y. et al. Laminin-332 coordinates mechanotransduction and growth cone bifurcation in sensory neurons. Nat. Neurosci. 14, 993–1000 (2011).

    Article  CAS  PubMed  Google Scholar 

  131. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Wu, H., Williams, J. & Nathans, J. Morphologic diversity of cutaneous sensory afferents revealed by genetically directed sparse labeling. Elife 1, e00181 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  133. Bourane, S. et al. Low-threshold mechanoreceptor subtypes selectively express MafA and are specified by Ret signaling. Neuron 64, 857–870 (2009).

    Article  CAS  PubMed  Google Scholar 

  134. Iggo, A. Cutaneous mechanoreceptors with afferent C fibres. J. Physiol. 152, 337–353 (1960).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. François, A. et al. The low-threshold calcium channel Cav3.2 determines low-threshold mechanoreceptor function. Cell Rep. 10, 370–382 (2015).

    Article  PubMed  CAS  Google Scholar 

  136. Wang, R. & Lewin, G. R. The Cav3.2 T-type calcium channel regulates temporal coding in mouse mechanoreceptors. J. Physiol. 589, 2229–2243 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Zotterman, Y. Touch, pain and tickling: an electro-physiological investigation on cutaneous sensory nerves. J. Physiol. 95, 1–28 (1939).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. 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).

    Article  CAS  PubMed  Google Scholar 

  139. Abraira, V. et al. The cellular and synaptic architecture of the mechanosensory dorsal horn. Cell 168, 295–310 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Hashimoto, K. Fine structure of perifollicular nerve endings in human hair. J. Invest. Dermatol. 59, 432–441 (1972).

    Article  CAS  PubMed  Google Scholar 

  141. Li, L. & Ginty, D. D. The structure and organization of lanceolate mechanosensory complexes at mouse hair follicles. eLife 3, e01901 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  142. 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).

    Article  CAS  PubMed  Google Scholar 

  143. Kaidoh, T. & Inoué, T. N-cadherin expression in palisade nerve endings of rat vellus hairs. J. Comp. Neurol. 506, 525–534 (2008).

    Article  CAS  PubMed  Google Scholar 

  144. Takahashi-Iwanaga, H. Three-dimensional microanatomy of longitudinal lanceolate endings in rat vibrissae. J. Comp. Neurol. 426, 259–269 (2000).

    Article  CAS  PubMed  Google Scholar 

  145. Fünfschilling, U. et al. TrkC kinase expression in distinct subsets of cutaneous trigeminal innervation and nonneuronal cells. J. Comp. Neurol. 480, 392–414 (2004).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  146. 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).

    CAS  PubMed  Google Scholar 

  147. 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).

    Article  PubMed  PubMed Central  Google Scholar 

  148. Chambers, M. R. & Iggo, A. Slowly-adapting cutaneous mechanoreceptors. J. Physiol. 192, 26P–27P (1967).

    CAS  PubMed  Google Scholar 

  149. 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).

    Article  CAS  PubMed  Google Scholar 

  150. Edin, B. B. Quantitative analysis of static strain sensitivity in human mechanoreceptors from hairy skin. J. Neurophysiol. 67, 1105–1113 (1992).

    Article  CAS  PubMed  Google Scholar 

  151. Fleming, M. S. & Luo, W. The anatomy, function, and development of mammalian Aβ low-threshold mechanoreceptors. Front. Biol. 8, 408–420 (2013).

    Article  CAS  Google Scholar 

  152. Halata, Z., Rettig, T. & Schulze, W. The ultrastructure of sensory nerve endings in the human knee joint capsule. Anat. Embryol. 172, 265–275 (1985).

    Article  CAS  Google Scholar 

  153. Rice, F. L. & Rasmusson, D. D. Innervation of the digit on the forepaw of the raccoon. J. Comp. Neurol. 417, 467–490 (2000).

    Article  CAS  PubMed  Google Scholar 

  154. 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).

    Article  CAS  PubMed  Google Scholar 

  155. 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).

    Article  CAS  Google Scholar 

  156. 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).

    Article  CAS  PubMed  Google Scholar 

  157. 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).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  158. Abdo, H. et al. Specialized cutaneous Schwann cells initiate pain sensation. Science 365, 695–699 (2019).

    Article  CAS  PubMed  Google Scholar 

  159. Moehring, F. et al. Keratinocytes mediate innocuous and noxious touch via ATP-P2X4 signaling. eLife 7, e31684 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  160. Winkelmann, R. K. The mucocutaneous end-organ: the primary organized sensory ending in human skin. AMA Arch. Derm. 76, 225–235 (1957).

    Article  CAS  PubMed  Google Scholar 

  161. Yamada, K. On the sensory nerve terminations in clitoris in human adult. Tohoku J. Exp. Med. 54, 163–174 (1951).

    Article  CAS  PubMed  Google Scholar 

  162. Gairns, F. W. The sensory nerve endings of the human palate. Q. J. Exp. Physiol. Cogn. Med. Sci. 40, 40–48 (1955).

    CAS  PubMed  Google Scholar 

  163. 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).

    Article  Google Scholar 

  164. Ohmori, D. Über die Entwicklung der Innervation der Genitalapparate als peripheren Aufnahmeapparat der genitalen Reflexe. Z. Anat. Entwicklungsgesch. 70, 347–410 (1924).

    Article  Google Scholar 

  165. Krause, W. Uber die Nervenendigung in den Geschlechtsorganen. Z. Nat. Medizin. XXVII, 86–88 (1866).

    Google Scholar 

  166. McNeilly, A. S. Physiology of lactation. J. Biosoc. Sci. 9, 5–21 (1977).

    Article  Google Scholar 

  167. Katz, D. The world of touch. Translated by Lester E. Krueger. (Routledge, 2016).

  168. 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).

    Article  CAS  Google Scholar 

  169. Lewicki, M. S. Efficient coding of natural sounds. Nat. Neurosci. 5, 356–363 (2002).

    Article  CAS  PubMed  Google Scholar 

  170. Leiser, S. C. & Moxon, K. A. Responses of trigeminal ganglion neurons during natural whisking behaviors in the awake rat. Neuron 53, 117–133 (2007).

    Article  CAS  PubMed  Google Scholar 

  171. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. 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).

    CAS  PubMed  Google Scholar 

  173. Severson, K. S. et al. Active touch and self-motion encoding by Merkel cell-associated afferents. Neuron 94, 666–676 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Olson, W. et al. Sparse genetic tracing reveals regionally specific functional organization of mammalian nociceptors. eLife 6, e29507 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  176. 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).

    Article  CAS  PubMed  Google Scholar 

  177. 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).

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank A. Emanuel, C. Santiago, C. Koutsioumpa, Q. Zhang, A. Tasnim and B. Lehnert for helpful comments on the manuscript. This work was supported by NIH grants NS97344 and AT011447 (D.D.G.), the Edward R. and Anne G. Lefler Center for Neurodegenerative Disorders (D.D.G.) and a Howard Hughes Medical Institute–Jane Coffin Childs Fellowship (A.H.). D.D.G. is an investigator of the Howard Hughes Medical Institute.

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Glossary

Integumentary system

An organ system that comprises the outermost layer of an animal’s body, including the skin, hair and nails.

Adaption

A decrease over time in a neuron’s response to a constant stimulus.

Static indentation of the skin

The application of a near constant force and pressure to the skin over a set period.

End organ structures

Specialized structures found at the terminal end of a sensory axon that contain both neuronal and non-neuronal cells and detect sensory stimuli, primarily mechanical forces.

Step indentation

A mechanical stimulus that abruptly increases from a constant baseline force to a larger constant force before abruptly returning to the baseline.

Receptive field

A defined area where physiological stimuli can evoke neural responses.

Lanceolate endings

A sensory ending that forms around hair follicles and runs parallel to the long axis of the hair shaft.

Touch dome

A sensory structure found in hairy skin containing a cluster of dozens to hundreds of Merkel cells and often just a single Aβ slowly adapting type 1 low-threshold mechanoreceptor.

Circumferential endings

A sensory ending that is situated in the circumferential collagen matrix and encircles the hair follicle just distal to the lanceolate endings.

Population coding

An encoding strategy where a stimulus is represented by the joint activities of a number of neurons.

Heminode

The first node of an axon situated just before the start of myelination.

Lamellae

The numerous, thin cellular processes that originate from lamellar cells and form a close association with the sensory terminals in end organ structures.

Turgor pressure

A force within a cell exerted on the plasma membrane and usually caused by osmotic flow.

Homotypic tiling

A phenomenon in which the arbors of a neuron innervate an area in a non-redundant or tiled manner with respect to the arbors of other neurons of the same type.

Caveolae

A special type of lipid raft that forms a small invagination (50–100 nm) in the plasma membrane, occurring due to the oligomerization of membrane-associated caveolin proteins.

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Handler, A., Ginty, D.D. The mechanosensory neurons of touch and their mechanisms of activation. Nat Rev Neurosci 22, 521–537 (2021). https://doi.org/10.1038/s41583-021-00489-x

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