The gentle touch receptors of mammalian skin

Abstract

The skin is our largest sensory organ, transmitting pain, temperature, itch, and touch information to the central nervous system. Touch sensations are conveyed by distinct combinations of mechanosensory end organs and the low-threshold mechanoreceptors (LTMRs) that innervate them. Here we explore the various structures underlying the diverse functions of cutaneous LTMR end organs. Beyond anchoring of LTMRs to the surrounding dermis and epidermis, recent evidence suggests that the non-neuronal components of end organs play an active role in signaling to LTMRs and may physically gate force-sensitive channels in these receptors. Combined with LTMR intrinsic properties, the balance of these factors comprises the response properties of mechanosensory neurons and, thus, the neural encoding of touch.

Fig. 1. LTMR innervation of glabrous skin

Glabrous skin is innervated by Aβ LTMRs, including Aβ SA1-LTMRs terminating in Merkel cells, Aβ SA2-LTMRs hypothesized to end in Ruffini endings, Aβ RA1-LTMRs innervating Meissner corpuscles, and Aβ RA2-LTMRs ending in Pacinian corpuscles. Green boxed regions are shown in greater detail in Fig. 3 (here, the letters “A,” “B,” and “C” correspond to panels with the same names in Fig. 3). SC, stratum corneum; SL, stratum lucidum; SG, stratum granulosum; SS, stratum spinosum; SB, stratum basale.

Fig. 2. LTMR innervation of hairy skin

Hairy skin in rodents is innervated by distinct combinations of LTMRs. Touch domes of Merkel cells and associated Aβ SA1-LTMRs are found above the level of the sebaceous glands of guard hair follicles. Guard hairs are also innervated by Aβ RA-LTMR lanceolate endings. Awl/auchene hairs are innervated by all three types of lanceolate-ending LTMRs: Aβ RA-LTMRs, Aδ-LTMRs, and C-LTMRs. Zigzag hairs, the most numerous, are innervated by Aδ-LTMRs and C-LTMRs. Circumferential endings encircle the longitudinal lanceolate endings of all three types of hair follicles. The white boxed region is shown in greater detail in Fig. 4.

Fig. 3. LTMR end organs of glabrous skin

(A) Merkel cells are located within the basal layer of the epidermis, innervated by a single Aβ SA1-LTMR. Cytoplasmic protrusions of the Merkel cell and hemidesmosomes physically link Merkel cells to surrounding epithelial cells. Dense-core vesicles are located inside the Merkel cell in close proximity to the enlarged axon terminal and are thought to be involved in signaling between the Merkel cell and the neurite. Recent evidence revealed Merkel cells to be mechanically sensitive and to play an active role in mechanotransduction (white arrows). (B) Meissner corpuscles are located within dermal papillae and are innervated by one or more Aβ RA1-LTMRs. The external capsule is linked to both the lamellar cells and the epidermis via collagen fibers. (C) Pacinian corpuscles are located in the deep dermis, contain layered lamellar cells, and are innervated by a single Aβ RA2-LTMR. Axonal protrusions project from the neurite into the cleft between inner-core lamellar cells and are thought to be the sites of generator potentials. Longitudinal and circumferential collagen fibers anchor the inner core and outer zone, respectively.

Fig. 4. LTMRs associated with mouse hair follicles

(A) Innervation pattern of Awl/auchene hair follicles. Terminal Schwann cells surround all three types of interdigitated lanceolate endings, as well as the circumferential ending(s). (B) Cross-sectional view of (A), based on electron microscopic analysis. Terminal Schwann cells surround lanceolate endings on either side, with a gap in coverage facing the hair follicle hair cells. Putative protein tethers may connect hair follicle epithelial cells with LTMRs and terminal Schwann cells, while both longitudinal and circumferential collagen fibers provide a supporting role.