Central and peripheral anatomy of slowly adapting type I low‐threshold mechanoreceptors innervating trunk skin of neonatal mice

Abstract

Despite intensive study, our understanding of the neuronal structures responsible for transducing the broad spectrum of environmental energies that impinge upon the skin has rested on inference and conjecture. This major shortcoming motivated the development of ex vivo somatosensory system preparations in neonatal mice in the hope that their small size might allow the peripheral terminals of physiologically identified sensory neurons to be labeled intracellularly for direct study. The present report describes the first such study of the peripheral terminals of four slowly adapting type I low-threshold mechanoreceptors (SAIs) that innervated the back skin of neonatal mice. In addition, this report includes information on the central anatomy of the same SAI afferents that were identified peripherally with both physiological and anatomical means, providing an essentially complete view of the central and peripheral morphology of individual SAI afferents in situ. Our findings reveal that SAIs in neonates are strikingly adult-like in all major respects. Afferents were exquisitely sensitive to mechanical stimuli and exhibited a distinctly irregular, slowly adapting discharge to stimulation of 1-4 punctate receptive fields in the skin. Their central collaterals formed transversely oriented and largely nonoverlapping arborizations limited to regions of the dorsal horn corresponding to laminae III-V. Their peripheral arborizations were restricted entirely within miniaturized touch domes, where they gave rise to expanded disc-like endings in close apposition to putative Merkel cells in basal epidermis. These findings therefore provide the first direct confirmation of the functional morphology of this physiologically unique afferent class.

Myelinated Skin Sensory Neurons Project Extensively throughout Adult Mouse Substantia Gelatinosa

“…With the exception of D-HFAs (see below), the central arbors of tactile afferents generally remained deep to the SG (e.g., Fig. 6G) and were identical in all major respects to published descriptions of the same afferent populations in mice (Woodbury et al, 2001;Koerber and Woodbury, 2002;Woodbury and Koerber, 2007) and cats (for review, see Brown, 1981); the central anatomy of mechano/cold afferents is the subject of a separate report (M. D. Boada and C. J. Woodbury, unpublished observations).…”

“…Interestingly, the central arbors of these nociceptors were often highly reminiscent of those from SAIs (Fig. 6G) (Koerber and Woodbury, 2002;Woodbury and Koerber, 2007), which cautions against inferring function on the basis of laminar termination patterns.…”

Voltage-activated ion channels and Ca2+-induced Ca2+ release shape Ca2+ signaling in Merkel cells

“…It is possible that protein expression changes in Merkel cells during this developmental period; however, as detailed below, our functional results from neonatal Merkel cells are entirely consistent with our histological results from juvenile mice. Moreover, SAI response thresholds, receptive field sizes, and firing patterns are remarkably similar in neonatal and adult mice [3].…”

“…They are one of the four major subtypes of touch receptors in primate fingertips and are critical for distinguishing the form of objects and fine textures [1]. SAI receptors, which comprise epidermal Merkel cells and somatosensory afferent terminals [2,3], are concentrated in areas of the skin that are highly touch-sensitive, including whisker follicles, fingertips, and touch domes (reviewed in [4]). …”

Long‐Term Effects of Neonatal Capsaicin Treatment on Intraepidermal Nerve Fibers and Keratinocyte Proliferation in Rat Glabrous Skin

“…Thus, the constant low levels of epidermal innervation in the treated rats may reflect a limited sprouting ability of the PGP þ or CGRP þ fibers that remain. Although the direct relation between peripheral arborization and specific sensory modalities is beginning to be understood, it is plausible that less branched arbor configuration of IENF in treated rats, may alter fiber excitability and circumscribe its area of activation (MacIver and Tanelian, 1993;Woodbury and Koerber, 2007). We note that the detection of noxious stimuli is impaired by capsaicin injection in human skin (Simone et al, 1998).…”