A large proportion of Aβ-LTMRs that innervate glabrous skin can be classified as slowly adapting, exhibiting maintained firing during sustained indentation. Slowly adapting responses can be further divided into two types that are common to most, if not all, vertebrate animal models (Wellnitz et al., 2010). Slowly adapting type I and II (SAI and SAII) responses are differentiated by the regularity of their static-phase firing rates, with SAI fibers exhibiting a more irregular selleck kinase inhibitor interspike interval than SAII units. They are also

differentiated by their tuning properties, tonic firing rates, and receptive field sizes. SAI-LTMRs and the Merkel Cell Complex. SAI-LTMRs innervate both hairy and glabrous skin

and respond to mechanical forces on the skin with a sustained and graded dynamic Epacadostat response followed by bursting at irregular intervals that is linearly correlated to indentation depths (Coleman et al., 2001, Harrington and Merzenich, 1970, Knibestöl and Vallbo, 1980, Wellnitz et al., 2010, Werner and Mountcastle, 1965 and Williams et al., 2010) (Table 1). SAI-LTMRs exhibit several remarkable physiological properties that endow them with the ability to transmit a highly acute spatial image of tactile stimuli. First, they respond maximally upon contact with corners, edges, and curvatures of objects with very low thresholds of skin displacement (less than 15 μm in humans). Second, they exhibit high spatial resolution (up to 0.5 mm for individual human SAI afferents), making them highly sensitive to stimulus position and velocity. SAI-LTMRs

are silent when skin is not stimulated and relatively insensitive to stretch of the skin or skin displacement adjacent to its receptive field, which typically ranges from 2–3 mm in humans. Merkel (1875) was the first to histologically describe an epidermal cell cluster forming Florfenicol contacts with afferent nerve fibers in vertebrate skin. A century later, the Merkel cell-neurite complex was described as the cellular substrate of SAI-LTMRs by meticulous histological analysis of SAI receptive fields mapped onto the skin (Halata et al., 2003, Iggo and Muir, 1969, Munger et al., 1971 and Woodbury and Koerber, 2007) (Figure 1). Merkel cell clusters are distributed throughout the skin, with each individual Merkel cell found in close apposition to one enlarged Aβ SAI-LTMR terminal. In humans, Merkel cells are enriched in highly sensitive areas of the skin, including glabrous skin of the fingers and lips (Figure 1A). They are also present in hairy skin, though at a lower density.