The peripheral nervous system detects different somatosensory stimuli including pain, temperature and touch. Merkel receptors are touch receptors composed of sensory afferents and Merkel cells. The role that Merkel cells play in light touch responses has been the center of controversy for over 100 years. We used Cre-loxP technology to conditionally delete the transcription factor Atoh1 from the body skin and foot pads of mice. Merkel cells are absent from these areas in Atoh1CKO animals. Ex vivo skin/nerve preparations from Atoh1CKO animals demonstrate complete loss of the characteristic neurophysiologic responses normally mediated by Merkel receptors. Merkel cells are therefore required for the proper encoding of Merkel receptor responses, suggesting that these cells form an indispensible part of the somatosensory system.

Touch is initiated by diverse somatosensory afferents that innervate the skin. The ability to manipulate and classify receptor subtypes is prerequisite for elucidating sensory mechanisms. Merkel cell-neurite complexes, which distinguish shapes and textures, are experimentally tractable mammalian touch receptors that mediate slowly adapting type I (SAI) responses. The assessment of SAI function in mutant mice has been hindered because previous studies did not distinguish SAI responses from slowly adapting type II (SAII) responses, which are thought to arise from different end organs, such as Ruffini endings. Thus we sought methods to discriminate these afferent types. We developed an epidermis-up ex vivo skin-nerve chamber to record action potentials from afferents while imaging Merkel cells in intact receptive fields. Using model-based cluster analysis, we found that two types of slowly adapting receptors were readily distinguished based on the regularity of touch-evoked firing patterns. We identified these clusters as SAI (coefficient of variation = 0.78 +/- 0.09) and SAII responses (0.21 +/- 0.09). The identity of SAI afferents was confirmed by recording from transgenic mice with green fluorescent protein-expressing Merkel cells. SAI receptive fields always contained fluorescent Merkel cells (n = 10), whereas SAII receptive fields lacked these cells (n = 5). Consistent with reports from other vertebrates, mouse SAI and SAII responses arise from afferents exhibiting similar conduction velocities, receptive field sizes, mechanical thresholds, and firing rates. These results demonstrate that mice, like other vertebrates, have two classes of slowly adapting light-touch receptors, identify a simple method to distinguish these populations, and extend the utility of skin-nerve recordings for genetic dissection of touch receptor mechanisms.

Touch is encoded by cutaneous sensory neurons with diverse morphologies and physiological outputs. How neuronal architecture influences response properties is unknown. To elucidate the origin of firing patterns in branched mechanoreceptors, we combined neuroanatomy, electrophysiology and computation to analyze mouse slowly adapting type I (SAI) afferents. These vertebrate touch receptors, which innervate Merkel cells, encode shape and texture. SAI afferents displayed a high degree of variability in touch-evoked firing and peripheral anatomy. The functional consequence of differences in anatomical architecture was tested by constructing network models representing sequential steps of mechanosensory encoding: skin displacement at touch receptors, mechanotransduction and action-potential initiation. A systematic survey of arbor configurations predicted that the arrangement of mechanotransduction sites at heminodes is a key structural feature that accounts in part for an afferent’s firing properties. These findings identify an anatomical correlate and plausible mechanism to explain the driver effect first described by Adrian and Zotterman.DOI: http://dx.doi.org/10.7554/eLife.01488.001

SignificanceThe earliest way humans can learn what their body is and where the outside world begins is through the tactile sense, especially through touch between parent and baby. In this study, we demonstrated differential processing of touch from self and others at cortical and spinal levels. Our results support top-down modulation of dorsal horn somatosensory processing, as recently shown in animal studies. We provide evidence that the individual self-concept relates to differential self- vs. other-processing in the tactile domain. Self- vs. other-distinction is necessary for successful social interaction with others and for establishing a coherent self. Our results suggest an association between impaired somatosensory processing and a dysfunctional self-concept, as seen in many psychiatric disorders.

Previous models of touch have linked skin mechanics to neural firing rate, neural dynamics to action potential elicitation, and mechanoreceptor populations to psychophysical discrimination. However, no one model spans all levels. The objective of work herein is to build a multi-level, computational model of tactile neurons embedded in cutaneous skin, and then validate its predictions of skin surface deflection, single-afferent firing to indenter shift, and population response for sphere discrimination. The model includes a 3D finite element representation of the distal phalange with hyper- and visco-elastic mechanics. Distributed over its surface, a population of receptor models is comprised of bi-phasic functions to represent Merkel cells’ transformation of stress/strain to membrane current and a leaky integrate-and-fire neuronal models to generate the timing of action potentials. After including neuronal noise, the predictions of two population encoding strategies (Gradient Sum and Euclidean Distance) are compared to psychophysical discrimination of spheres. Results indicate that predicted skin surface deflection matches Srinivasan's observations for 50 micron and 3.17 mm diameter cylinders and single-afferent responses achieve R2=0.81 when compared to Johnson’s recordings. Discrimination results correlate with Goodwin’s experiments, whereby 287 and 365 m−1 spheres are more discriminable than 287 and 296 m−1.