How many hair follicles are innervated by one afferent axon? A confocal microscopic analysis of palisade endings in the auricular skin of thy1-YFP transgenic mouse

Abstract

Hairs are known as a sensory apparatus for touch. Their follicles are innervated predominantly by palisade endings composed of longitudinal and circumferential lanceolate endings. However, little is known as to how their original primary neurons make up a part of the ending. In this study, innervation of the palisade endings was investigated in the auricular skin of thy1-YFP transgenic mouse. Major observations were 1) Only a small portion of PGP9.5-immunopositive axons showed YFP-positivity, 2) All of thy1-YFP-positive sensory axons were thick and myelinated, 3) Individual thy1-YFP-positive trunk axons innervated 4–54 hair follicles, 4) Most palisade endings had a gap of lanceolate ending arrangement, 5) PGP9.5-immunopositive 10–32 longitudinal lanceolate endings were closely arranged. Only a part of them were thy1-YFP-positive axons that originated from 1–3 afferents, and 6) Single nerve bundles of the dermal nerve network included both bidirectional afferents. Palisade endings innervated by multiple sensory neurons might be highly sensitive to hair movement.

The Sensory Neurons of Touch

“…With the recent development of mouse genetic tools, anatomical features of LTMRs, such as receptive fields, can now be defined by the number of hair follicles that they associate with. We now appreciate the existence of a variety of anatomical peripheral receptive fields formed by Aβ hair follicle afferents, which can range from single hair follicles to clusters of adjacent hair follicles (Li et al, 2011; Suzuki et al, 2012; Wu et al, 2012). …”

“…All three types of hair follicles in the rodent also receive circumferential endings, which wrap two or more times around the palisades of the longitudinal LTMR endings (Millard and Woolf, 1988)(Figure 1B, Figure 3E). Circumferential hair follicle afferents have not yet been characterized physiologically, although at the molecular level they seem to fall into two main categories; those that are neurofilament 200 positive and presumed to originate from large diameter sensory neurons, and those that expresses the nociceptive marker CGRP and are presumed to play a role in nociception (Lawson et al, 2002; Peters et al, 2002; Stucky et al, 1998; Suzuki et al, 2012; Woo et al, 2012). A major current challenge is defining the physiological properties of the neurons that form these two neurochemically distinct circumferential ending types.…”

The specification and wiring of mammalian cutaneous low‐threshold mechanoreceptors

“…They form a palisade of endings surrounding the follicle, with each ending composed of a flattened stack of Schwann cells innervated by an Aβ axonal branch (Figure ). The palisades surrounding one hair follicle can be innervated by multiple individual axonal fibers and individual axons can innervate multiple hair follicles . In addition, Aβ lanceolate endings can coinnervate hair follicles along with lanceolate endings from Aδ‐ and/or C‐LTMRs .…”

“…This is because the analysis of mutant phenotypes for lanceolate endings is more difficult due to the presence of three types of lanceolate endings (Aβ, Aδ, and C) intermingled around individual hair follicles . Additionally, a high degree of variability exists in both the number of endings surrounding one follicle and the number of follicles innervated by one Aβ‐, Aδ‐, or C‐LTMR axon, further complicating analysis of mutant phenotypes. For example, although neural crest conditional deletion of either Ret or Ntrk2 severely affects Meissner's and Pacinian corpuscle development, Aβ lanceolate endings still appear to be present in the hairy skin of these mice .…”

The anatomy, function, and development of mammalian Aβ low-threshold mechanoreceptors

“…Axonal spikes protruding through the sheath where the two Schwann cell faces meet contact both the hair follicle and the surrounding connective tissue (Munger and Ide, 1988). Sparse genetic labeling of hair follicle innervating axons shows that the lanceolate endings which make up each palisade structure are innervated by more than one sensory afferent, and that individual mechanoreceptive neurons can innervate lanceolate endings surrounding multiple hair follicles (Suzuki et al, 2012). …”