Touch Receptors Undergo Rapid Remodeling in Healthy Skin

Abstract

Summary Sensory tissues exposed to the environment, such as skin, olfactory epithelia and taste buds, continuously renew; therefore, peripheral neurons must have mechanisms to maintain appropriate innervation patterns. Although somatosensory neurons regenerate after injury, little is known about how these neurons cope with normal target-organ changes. To elucidate neuronal plasticity in healthy skin, we analyzed the structure of Merkel-cell afferents, which are gentle touch receptors, during skin remodeling that accompanies mouse hair-follicle regeneration. The number of Merkel cells is reduced by 90% and axonal arbors are simplified during active hair growth. These structures rebound within just days. Computational modeling predicts that Merkel-cell changes are probabilistic but myelinated branch stability depends on Merkel-cell inputs. Electrophysiology and behavior demonstrate that tactile responsiveness is less reliable during active growth than in resting skin. These results reveal that somatosensory neurons display structural plasticity at the cost of impairment in the reliability of encoding gentle touch.

A discrete-event simulation approach to identify rules that govern arbor remodeling for branching cutaneous afferents in hairy skin

“…Based on the prior modeling effort (Marshall 2016), a preliminary set of rules was developed, which have been modified in the present work to come from a bottom-up perspective as shown in Table 1. In general, we check first the state of a heminode by checking the associated terminal branches and Merkel cells.…”

“…Sensory receptors include cutaneous light touch afferents as well as those signaling information regarding proprioception, chemoreception and pain. Both the sensory receptors and the skin are continually renewing and remodeling to maintain barrier in normal states and after injury (Chung 2010; Marshall 2016; Müller-Röver 2001; Rajan 2003). In hairy skin, Merkel cell nerve endings are clustered into specialized epithelial structures called “touch domes” Plikus 2008).…”

“…A Merkel cell’s connection to or removal from a terminal neurite, and neurites from heminodes, have been observed to follow trends specific to the stages of the hair cycle in the mouse (Marshall 2016). In particular, as mice age, multiple synchronized hair cycles are observed, where the hair of the animal changes over its entire body in a wave-like fashion (Müller-Röver 2001).…”

“…Moreover, despite instances of discrete event simulation (DES) models in biological research, there are still very few published examples of comprehensively validated models. As such, our group recently built a computational model to test an initial set of rules governing arbor remodeling mechanisms (Marshall 2016). With its top down approach, population statistics from observed data were used to construct the computational model.…”

“…While the study (Marshall 2016) contributed to explaining rules that govern Merkel cell-neurite (or arbor) remodeling processes, those computational models have several limitations. For instance, the individual end organ constituents of Merkel cells, terminal neurites and heminodes were not traceable between phases of the hair cycle.…”