Like other hairy skin LTMRs, C-LTMRs form longitudinal lanceolate endings around hair follicles and, like Aδ-LTMRs,

these develop only around awl/auchene and zigzag hair CP-673451 supplier follicles ( Figure 1B). This observation was surprising, because historically in the cat and rat C-LTMRs did not respond to movement of individual hair follicles and, therefore, were not thought to be hair receptors like Aβ RA-LTMRs found in hairy skin ( Bessou et al., 1971). Remarkably, C- and Aδ-LTMR longitudinal lanceolate endings associated with awl/auchene and zigzag hair follicles are interdigitated ( Figure 1B). C-LTMRs in the mouse also uniquely express the vesicular glutamate transporter VGLUT3, and behavioral deficits in Vglut3 knockout animals have suggested that C-LTMRs may AZD2281 in vivo be required for injury-induced mechanical hypersensitivity ( Seal et al., 2009), though this is controversial ( Lou et al., 2013). Recently, MRGPRB4-expressing nonpeptidergic nociceptors, a morphologically and anatomically distinct class of C fibers of unknown physiological properties, have been implicated in pleasant touch. Similar to TH and VGLUT3-expressing C-LTMRs,

MRGPRB4+ C fibers innervate only hairy skin ( Liu et al., 2007 and Vrontou et al., 2013). Thus, multiple C fiber subtypes appear to contribute STK38 to behavioral responses and the perception of light touch. Hair Follicle Afferents Are Complex Both in Form and Function. The density and intricate innervation patterns of hair follicles and the sheer extent of hairy skin areas of mammals dictate that the major portion of our primary somatosensory neurons is devoted to hairy skin. How are the endings of hairy skin LTMRs organized and does this provide insight into larger questions of how light touch information is coded? The most abundant type of hair follicle in the mouse, accounting for 76% of follicles of the coat, is the zigzag hair follicle, which receives both C- and Aδ-LTMR

lanceolate endings in a remarkable interdigitated manner. Awl/auchene hair follicles, representing roughly 23% of the follicles, are triply innervated by interdigitating endings of Aβ-RA-LTMRs, Aδ-LTMRs, and C-LTMRs. Guard hairs, the longest but least abundant, representing just 1% of hair follicles, are innervated by Aβ RA-LTMR lanceolate endings and are associated with Aβ-SAI-LTMRs that innervate touch domes (Li et al., 2011) (Figures 1B and 3E). 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) (Figures 1B and 3E).