The Functional Organization of Cutaneous Low-Threshold Mechanosensory Neurons

Abstract

Summary Innocuous touch of the skin is detected by distinct populations of low-threshold mechanoreceptors (LTMRs), which are classified as Aβ-, Aδ- and C-LTMRs. Here, we report genetic labeling of LTMR subtypes and visualization of their relative patterns of axonal endings in hairy skin and the spinal cord. We found that each of the three major hair follicle types of trunk hairy skin; guard, awl/auchene, and zigzag hairs, is innervated by a unique and invariant combination of LTMRs; thus, each hair follicle type is a functionally distinct mechanosensory end organ. Moreover, the central projections of Aβ-, Aδ- and C-LTMRs that innervate the same or adjacent hair follicles form narrow LTMR columns in the dorsal horn. These findings support a model of mechanosensation in which the activities of Aβ-, Aδ- and C-LTMRs are integrated within dorsal horn LTMR columns and processed into outputs that underlie the perception of myriad touch sensations.

Somatosensory neuron types identified by high-coverage single-cell RNA-sequencing and functional heterogeneity

“…Our analysis supports the notion that the TH-positive DRG neuron functions as C-LTMR [2,49]. C3 expresses Th, Fam19a4, Cpne6 and Piezo2 [50].…”

“…Large DRG neurons transmit mechanoreceptive and proprioceptive signals via thickly myelinated afferents (Aβ-fibers) to spinal lamina III-V [1]. Traditionally, small neurons have been classified into three subsets: isolectin B4 (IB4)-positive (non-peptidergic, NP) subset, peptidergic (PEP, IB4 negative) subset expressing neuropeptide substance P and calcitonin gene-related peptide (CGRP), and tyrosine hydroxylase (TH)-expressing subset, while large neurons express neurofilament 200 (NF200) [2][3][4][5].…”

Aberrant Synaptic Integration in Adult Lamina I Projection Neurons Following Neonatal Tissue Damage

“…Ex vivo phenotyping of sensory neurons suggests that slowly adapting A␤ LTMRs project to lamina II i -V of the dorsal horn in adult mice (Woodbury and Koerber, 2007). Similarly, recent genetic labeling of the rapidly adapting A␤ LTMR population via the Npy2r promoter revealed central terminations that were restricted to laminae III-V (Li et al, 2011). This is in general agreement with our observations that axonal boutons immunopositive for VGLUT1, a marker of large, myelinated proprioceptors and innocuous mechanoreceptors Alvarez et al, 2004;Yasaka et al, 2014), rarely contacted adult lamina I projection neurons (Fig.…”

Responses of hair follicle–associated structures to loss of planar cell polarity signaling

“…Like primary auditory hair cells, with which they share a number of molecular attributes, Merkel cells appear to act as mechanosensors (6). Hair follicles are in direct contact with a variety of morphologically distinct cutaneous sensory afferents (7,8). For example, one subtype contacts the follicle with a group of 5-10 extended rods aligned along the follicle axis (lanceolate endings), and a second subtype extends branches that wrap multiple times around the follicle (9).…”