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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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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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