Merkel Cell-neurite Complexes Research Articles

Acid-sensing ion channels drive the generation of tactile impulses in Merkel cell-neurite complexes of the glabrous skin of rodent hindpaws.

Merkel cell-neurite complexes (MNCs) are enriched in touch-sensitive areas, including whisker hair follicles and the glabrous skin of the rodent's paws, where tactile stimulation elicits slowly adapting type 1 (SA1) tactile impulses to encode for the sense of touch. Recently, we have shown with rodent whisker hair follicles that SA1 impulses are generated through fast excitatory synaptic transmission at MNCs and driven by acid-sensing ion channels (ASICs). However, it is currently unknown whether, besides whisker hair follicles, ASICs also play an essential role in generating SA1 impulses from MNCs of other body parts in mammals. In the present study, we attempted to address this question by using the skin-nerve preparations made from the hindpaw glabrous skin and tibial nerves of both male and female rodents and applying the pressure-clamped single-fiber recordings. We showed that SA1 impulses elicited by tactile stimulation to the rat hindpaw glabrous skin were largely diminished in the presence of amiloride and diminazene, two ASIC channel blockers. Furthermore, using the hindpaw glabrous skin and tibial nerve preparations made from the mice genetically deleted of ASIC3 channels (ASIC3-/-), we showed that the frequency of SA1 impulses was significantly lower in ASIC3-/- mice than in littermate wildtype ASIC3+/+ mice, a result consistent with the pharmacological experiments with ASIC channel blockers. Our findings suggest that ASIC channels are essential for generating SA1 impulses to underlie the sense of touch in the glabrous skin of rodent hindpaws.Significance Statement Merkel cell-neurite complexes (MNCs) are enriched in touch-sensitive areas, including whisker hair follicles and the glabrous skin of the rodent's paws, where tactile stimulation elicits slowly adapting type 1 (SA1) tactile impulses to encode for the sense of touch. Here, using the skin-nerve preparations made from the hindpaw glabrous skin and tibial nerves of rodents and applying the pressure-clamped single-fiber recordings, we have demonstrated that ASIC channels are essential for generating SA1 impulses at MNCs in the glabrous skin of rodent hindpaws. Thus, ASIC channels at MNCs may play a key role in the sense of touch to the skin of mammals.

PHeeling the pHorce

In this issue of Neuron, Yamada etal.1 show that fast excitatory neurotransmission by protons acting at acid-sensing ion channels (ASICs) mediates mechanical force-evoked signaling at the Merkel cell-neurite complex, contributing to mammalian tactile discrimination.

ASICs mediate fast excitatory synaptic transmission for tactile discrimination

Tactile discrimination, the ability to differentiate objects' physical properties such as texture, shape, and edges, is essential for environmental exploration, social interaction, and early childhood development. This ability heavily relies on Merkel cell-neurite complexes (MNCs), the tactile end-organs enriched in the fingertips of humans and the whisker hair follicles of non-primate mammals. Although recent studies have advanced our knowledge on mechanical transduction in MNCs, it remains unknown how tactile signals are encoded at MNCs. Here, using rodent whisker hair follicles, we show that tactile signals are encoded at MNCs as fast excitatory synaptic transmission. This synaptic transmission is mediated by acid-sensing ion channels (ASICs) located on the neurites of MNCs, with protons as the principal transmitters. Pharmacological inhibition or genetic deletion of ASICs diminishes the tactile encoding at MNCs and impairs tactile discrimination in animals. Together, ASICs are required for tactile encoding at MNCs to enable tactile discrimination in mammals.

Sensory Nerve Sprouting into Human Skin Explants Confers Improved Survival to Merkel Cells Independent of Merkel Cell–Neurite Complexes

Sensory Nerve Sprouting into Human Skin Explants Confers Improved Survival to Merkel Cells Independent of Merkel Cell–Neurite Complexes

Dermal appendage-dependent patterning of zebrafish atoh1a+ Merkel cells.

Touch system function requires precise interactions between specialized skin cells and somatosensory axons, as exemplified by the vertebrate mechanosensory Merkel cell-neurite complex. Development and patterning of Merkel cells and associated neurites during skin organogenesis remain poorly understood, partly due to the in utero development of mammalian embryos. Here, we discover Merkel cells in the zebrafish epidermis and identify Atonal homolog 1a (Atoh1a) as a marker of zebrafish Merkel cells. We show that zebrafish Merkel cells derive from basal keratinocytes, express neurosecretory and mechanosensory machinery, extend actin-rich microvilli, and complex with somatosensory axons, all hallmarks of mammalian Merkel cells. Merkel cells populate all major adult skin compartments, with region-specific densities and distribution patterns. In vivo photoconversion reveals that Merkel cells undergo steady loss and replenishment during skin homeostasis. Merkel cells develop concomitant with dermal appendages along the trunk and loss of Ectodysplasin signaling, which prevents dermal appendage formation, reduces Merkel cell density by affecting cell differentiation. By contrast, altering dermal appendage morphology changes the distribution, but not density, of Merkel cells. Overall, our studies provide insights into touch system maturation during skin organogenesis and establish zebrafish as an experimentally accessible in vivo model for the study of Merkel cell biology.

Percutaneous Removal of a Foreign Body From the Distal Phalanx Using a 14 Gauge Needle and Fluoroscopy

Percutaneous Removal of a Foreign Body From the Distal Phalanx Using a 14 Gauge Needle and Fluoroscopy

Psoriasis, Is It a Microdamage of Our "Sixth Sense"? A Neurocentric View.

Psoriasis is considered a multifactorial and heterogeneous systemic disease with many underlying pathologic mechanisms having been elucidated; however, the pathomechanism is far from entirely known. This opinion article will demonstrate the potential relevance of the somatosensory Piezo2 microinjury-induced quad-phasic non-contact injury model in psoriasis through a multidisciplinary approach. The primary injury is suggested to be on the Piezo2-containing somatosensory afferent terminals in the Merkel cell–neurite complex, with the concomitant impairment of glutamate vesicular release machinery in Merkel cells. Part of the theory is that the Merkel cell–neurite complex contributes to proprioception; hence, to the stretch of the skin. Piezo2 channelopathy could result in the imbalanced control of Piezo1 on keratinocytes in a clustered manner, leading to dysregulated keratinocyte proliferation and differentiation. Furthermore, the author proposes the role of mtHsp70 leakage from damaged mitochondria through somatosensory terminals in the initiation of autoimmune and autoinflammatory processes in psoriasis. The secondary phase is harsher epidermal tissue damage due to the primary impaired proprioception. The third injury phase refers to re-injury and sensitization with the derailment of healing to a state when part of the wound healing is permanently kept alive due to genetical predisposition and environmental risk factors. Finally, the quadric damage phase is associated with the aging process and associated inflammaging. In summary, this opinion piece postulates that the primary microinjury of our “sixth sense”, or the Piezo2 channelopathy of the somatosensory terminals contributing to proprioception, could be the principal gateway to pathology due to the encroachment of our preprogrammed genetic encoding.

Synaptophysin is a selective marker for axons in human cutaneous end organ complexes

BackgroundSmall clear synaptic-like vesicles fill axon terminals of mechanoreceptors. Their functional significance is controversial and probably includes release of neurotransmitters from afferent axon terminals. Synaptophysin, a major protein of the synaptic vesicle membrane, is present in presynaptic endings of the central and peripheral nervous systems. It is also expressed in mechanosensory neurons which extend into skin forming sensory corpuscles. Nevertheless, synaptophysin occurrence in these structures has never been investigated. MethodsHere we used immunohistochemistry to detect synaptophysin in adult human dorsal root ganglia, cutaneous Meissner and Pacinian corpuscles and Merkel cell-neurite complexes from foetal to elderly period. Moreover, we analyzed whether synaptophysin co-localizes with the mechano-gated protein PIEZO2. ResultsSynaptophysin immunoreactivity was observed in primary sensory neurons (36 ± 6%) covering the entire soma size ranges. Axons of Meissner’s and Pacinian corpuscles were positive for synaptophysin from 36 and 12 weeks of estimated gestational age respectively, to 72 years old. Synaptophysin was also detected in Merkel cells (from 14 weeks of estimated gestational age to old age). Additionally in adult skin, synaptophysin and PIEZO2 co-localized in the axon of Meissner and Pacinian corpuscles, Merkel cells as well as in some axons of Merkel cell-neurite complexes. ConclusionPresent results demonstrate that a subpopulation of primary sensory neurons and their axon terminals forming cutaneous sensory corpuscles contain synaptophysin, a typical presynaptic vesicle protein. Although the functional relevance of these findings is unknown it might be related to neurotransmission mechanisms linked to mechanotransduction.

Effects of Oxaliplatin on Facial Sensitivity to Cool Temperatures and TRPM8 Expressing Trigeminal Ganglion Neurons in Mice.

The chemotherapeutic agent oxaliplatin is commonly used to treat colorectal cancer. Although effective as a chemotherapeutic, it frequently produces painful peripheral neuropathies. These neuropathies can be divided into an acute sensitivity to cool temperatures in the mouth and face, and chronic neuropathic pain in the limbs and possible numbness. The chronic neuropathy also includes sensitivity to cool temperatures. Neurons that detect cool temperatures are reported to utilize Transient Receptor Potential Cation Channel, Subfamily M, Member 8 (TRPM8). Therefore, we investigated the effects of oxaliplatin on facial nociception to cool temperatures (18°C) in mice and on TRPM8 expressing trigeminal ganglion (TRG) neurons. Paclitaxel, a chemotherapeutic that is used to treat breast cancer, was included for comparison because it produces neuropathies, but acute cool temperature sensitivity in the oral cavity or face is not typically reported. Behavioral testing of facial sensitivity to 18°C indicated no hypersensitivity either acutely or chronically following either chemotherapeutic agent. However, whole cell voltage clamp experiments in TRPM8 expressing TRG neurons indicated that both oxaliplatin and paclitaxel increased Hyperpolarization-Activated Cyclic Nucleotide-Gated channel (HCN), voltage gated sodium channel (Nav), and menthol evoked TRPM8 currents. Voltage gated potassium channel (Kv) currents were not altered. Histological examination of TRPM8 fibers in the skin of the whisker pads demonstrated that the TRPM8 expressing axons and possible Merkel cell-neurite complexes were damaged by oxaliplatin. These findings indicate that oxaliplatin induces a rapid degeneration of TRG neuron axons that express TRPM8, which prevents evoked activation of the sensitized neurons and likely leads to reduced sensitivity to touch and cool temperatures. The changes in HCN, Nav, and TRPM8 currents suggest that spontaneous firing of action potentials may be increased in the deafferented neurons within the ganglion, possibly producing spontaneously induced cooling or nociceptive sensations.

The acquisition of mechanoreceptive competence by human digital Merkel cells and sensory corpuscles during development: An immunohistochemical study of PIEZO2

BackgroundPIEZO2 is a transmembrane protein forming part of an ion channel required for mechanotransduction. In humans, PIEZO2 is present in axon terminals of adult Meissner and Pacinian corpuscles, as well as Merkel cells in Merkel cell-neurite complexes. MethodsTo study the acquisition of functional capability for mechanotransduction of developing type I slowly adapting low-threshold mechanoreceptors, i.e., Merkel cell-neurite complexes, a battery of immunohistochemical and immunofluorescence techniques was performed on human skin specimens covering the whole development and growth, from 11 weeks of estimated gestational age to 20 years of life. In addition, developmental expression of PIEZO2 type I (Meissner’s corpuscles) and type II (Pacinian corpuscles) rapidly adapting mechanoreceptors was studied in parallel. ResultsThe first evidence of Merkel cells showing the typical morphology and placement was at 13 weeks of estimated gestation age, and at this time positive immunoreactivity for PIEZO2 was achieved. PIEZO2 expression in axons terminals started at 23 WEGA in Pacinian corpuscles and at 36 WEGA in the case of Meissner corpuscles. The occurrence of PIEZO2 in Merkel cells, Meissner and Pacinian corpuscles was maintained for all the time investigated. Interestingly PIEZO2 was absent in most Aβ type I slowly adapting low-threshold mechanoreceptors that innervate MC while it was regularly present in most Aβ type I and type II rapidly adapting low-threshold mechanoreceptors that supplies Meissner and Pacinian corpuscles. ConclusionThe present results provide evidence that human cutaneous mechanoreceptors could perform mechanotransduction already during embryonic development.

Merkel receptor-inspired integratable and biocompatible pressure sensor with linear and ultrahigh sensitive response for versatile applications

Integrating high sensitivity with broad linear range for pressure sensors enables accurate data acquisition and avoids additional complex signal processing, bringing e-skins great liberation especially for high-precision applications such as medical diagnostic, bio-signal monitoring and human–machine interaction. However, it still remains a critical challenge to ease the conflicts between high sensitivity and high linearity via traditional micro-engineered strategies. Here, inspired by the sensing principle of Merkel receptors underlying epidermis, we propose a strategy of orthogonal knitted threads-induced local stress concentration that can significantly broaden the linear range of the pressure sensors without sacrificing the ultrahigh sensitivity. The high-modulus Ag/nylon threads orthogonally knitted onto low-modulus micro-structured non-woven fabrics generate enhanced local stress concentration at the intersections and facilitate the amplification and transfer of the pressure signals, achieving simultaneous enhancement of sensitivity (8.59 kPa−1) and linearity (0.2–400 kPa). With its miniaturable, integratable and biocompatible characteristics, as proof-of-concept demonstration, the sensors have been exploited for handwriting recognition, human–machine interaction and cardiovascular assessment.

329 In vitro co-culture models of merkel cell-neurite complex in touch domes

Touch dome, a specialized epidermal structure comprised from mechanosensory Merkel cell-neurite complex, has been known to change their numbers in the spontaneous hair cycle in mice. At the anagen phase, the number of Merkel cells are dramatically reduced with the loss of terminal neurites in touch dome afferents, indicating neuronal plasticity in healthy skin during hair-follicle regeneration. In this study, we focused on the role of Merkel cell-neurite complex in hair growth on the basis of the reports that the mechanical stimulation of human scalp by a massage improves hair thickness.

An Enhanced FingerVision for Contact Spatial Surface Sensing

Vision-based tactile sensor is a promising solution for tactile sensing. In this paper, we customized FingerVision sensor with multi-layer structure and biomimetic features, and used it to verify a two-step spatial surface sensing method. For the custom sensor, the multi-layer structure imitated the skin and tissue, and the sensing area and frequency range were consistent with the Meissner's corpuscles and Merkel discs. The two-step sensing method was verified through spatial reconstruction and surface recognition. First, we employed the integration method for surface reconstruction based on the gradients estimated from the marker displacements. The similarity between the reconstructed and the actual contact surface was 85.33% in average according to the evaluation on heights. Then we improved the features by correcting the marker displacements according to the boundary condition during surface reconstruction for surface recognition implementing K-Nearest Neighbor (KNN) algorithm. The accuracy was up to 99.26% when the training set was only 15% for 19 surface classes. While with the features extracted from the original coordinates, the accuracy was only 95.58%. The two-step sensing method implied that the surface reconstruction and recognition were related, and the reconstruction step indeed helped to the recognition. Additionally, the excellent recognition capability indicated the practical value of our custom sensor and the feature processing method in surface recognition through touch.

Sex-Dependent Reduction in Mechanical Allodynia in the Sural-Sparing Nerve Injury Model in Mice Lacking Merkel Cells.

Innocuous touch sensation is mediated by cutaneous low-threshold mechanoreceptors (LTMRs). Aβ slowly adapting type I (SAI) neurons constitute one LTMR subtype that forms synapse-like complexes with associated Merkel cells in the basal skin epidermis. Under healthy conditions, these complexes transduce indentation and pressure stimuli into Aβ SAI LTMR action potentials that are transmitted to the CNS, thereby contributing to tactile sensation. However, it remains unknown whether this complex plays a role in the mechanical hypersensitivity caused by peripheral nerve injury. In this study, we characterized the distribution of Merkel cells and associated afferent neurons across four diverse domains of mouse hind paw skin, including a recently described patch of plantar hairy skin. We also showed that in the spared nerve injury (SNI) model of neuropathic pain, Merkel cells are lost from the denervated tibial nerve territory but are relatively preserved in nearby hairy skin innervated by the spared sural nerve. Using a genetic Merkel cell KO mouse model, we subsequently examined the importance of intact Merkel cell-Aβ complexes to SNI-associated mechanical hypersensitivity in skin innervated by the spared neurons. We found that, in the absence of Merkel cells, mechanical allodynia was partially reduced in male mice, but not female mice, under sural-sparing SNI conditions. Our results suggest that Merkel cell-Aβ afferent complexes partially contribute to mechanical allodynia produced by peripheral nerve injury, and that they do so in a sex-dependent manner.SIGNIFICANCE STATEMENT Merkel discs or Merkel cell-Aβ afferent complexes are mechanosensory end organs in mammalian skin. Yet, it remains unknown whether Merkel cells or their associated sensory neurons play a role in the mechanical hypersensitivity caused by peripheral nerve injury. We found that male mice genetically lacking Merkel cell-Aβ afferent complexes exhibited a reduction in mechanical allodynia after nerve injury. Interestingly, this behavioral phenotype was not observed in mutant female mice. Our study will facilitate understanding of mechanisms underlying neuropathic pain.

Somatosensory innervation of healthy human oral tissues.

The oral somatosensory system relays essential information about mechanical stimuli to enable oral functions such as feeding and speech. The neurochemical and anatomical diversity of sensory neurons across oral cavity sites have not been systematically compared. To address this gap, we analyzed healthy human tongue and hard-palate innervation. Biopsies were collected from 12 volunteers and underwent fluorescent immunohistochemistry (≥2 specimens per marker/structure). Afferents were analyzed for markers of neurons (βIII tubulin), myelinated afferents (neurofilament heavy, NFH), and Merkel cells and taste cells (keratin 20, K20). Hard-palate innervation included Meissner corpuscles, glomerular endings, Merkel cell-neurite complexes, and free nerve endings. The organization of these somatosensory endings is reminiscent of fingertips, suggesting that the hard palate is equipped with a rich repertoire of sensory neurons for pressure sensing and spatial localization of mechanical inputs, which are essential for speech production and feeding. Likewise, the tongue is innervated by afferents that impart it with exquisite acuity and detection of moving stimuli that support flavor construction and speech. Filiform papillae contained end bulbs of Krause, as well as endings that have not been previously reported, including subepithelial neuronal densities, and NFH+ neurons innervating basal epithelia. Fungiform papillae had Meissner corpuscles and densities of NFH+ intraepithelial neurons surrounding taste buds. The differing compositions of sensory endings within filiform and fungiform papillae suggest that these structures have distinct roles in mechanosensation. Collectively, this study has identified previously undescribed neuronal endings in human oral tissues and provides an anatomical framework for understanding oral mechanosensory functions.

Human Touch Receptors Are Sensitive to Spatial Details on the Scale of Single Fingerprint Ridges.

Fast-adapting type 1 (FA-1) and slowly-adapting type 1 (SA-1) first-order tactile neurons provide detailed spatiotemporal tactile information when we touch objects with fingertips. The distal axon of these neuron types branches in the skin and innervates many receptor organs associated with fingerprint ridges (Meissner corpuscles and Merkel cell neurite complexes, respectively), resulting in heterogeneous receptive fields whose sensitivity topography includes many highly sensitive zones or "subfields." In experiments on humans of both sexes, using raised dots that tangentially scanned the receptive field we examined the spatial acuity of the subfields of FA-1 and SA-1 neurons and its constancy across scanning speed and direction. We report that the sensitivity of the subfield arrangement for both neuron types on average corresponds to a spatial period of ∼0.4 mm and provide evidence that a subfield's spatial selectivity arises because its associated receptor organ measures mechanical events limited to a single papillary ridge. Accordingly, the sensitivity topography of a neuron's receptive fields is quite stable over repeated mappings and over scanning speeds representative of real-world hand use. The sensitivity topography is substantially conserved also for different scanning directions, but the subfields can be relatively displaced by direction-dependent shear deformations of the skin surface.SIGNIFICANCE STATEMENT The branching of the distal axon of human first-order tactile neurons with receptor organs associated with fingerprint ridges (Meissner and Merkel end-organs) results in cutaneous receptive fields composed of several distinct subfields spread across multiple ridges. We show that the subfields' spatial selectivity typically corresponds to the dimension of the ridges (∼0.4 mm) and a neuron's subfield layout is well preserved across tangential movement speeds and directions representative of natural use of the fingertips. We submit that the receptor organs underlying subfields essentially measure mechanical events at individual ridges. That neurons receive convergent input from multiple subfields does not preclude the possibility that spatial details can be resolved on the scale of single fingerprint ridges by a population code.

Immunohistochemical Analysis of Prurigo Nodularis in 209 Patients: Clinicopathological Analysis between Atopic and Non-Atopic Patients and between Treatment Response Groups.

BackgroundPrurigo nodularis (PN) is a highly pruritic disease that significantly impairs patient quality of life. Although the mechanism that causes pruritus is not clear, one hypothesis argues that neural hyperplasia, mast cell, and Merkel cell neurite complexes may be associated with PN pathogenesis.ObjectiveThe objective of this study was to analyze whether special staining outcomes differed depending on the presence of atopic dermatitis (AD) and treatment response.MethodsA total of 209 patients diagnosed with PN was analyzed retrospectively. Patients were divided into two groups according to presence or past history of AD and by treatment response. Histopathologic features were obtained using the following stains: Giemsa, S-100, neuron-specific enolase, cytokeratin (CK)-20, CAM5.2, and CK8/CK18.ResultsA total of 126 patients (60.29%) had AD, and 68 (32.54%) showed clinical improvement. There were no statistically significant differences in the staining results between the PN groups with AD (PN c AD) and without AD (PN s AD). Additionally, there were no statistically significant differences in staining results between the improved and non-improved groups.ConclusionImplementing the special stains helped to identify PN pathogenesis. Because there were no statistically significant differences in the special stain results between the improved and non-improved groups, we conclude that mast cell proliferation, neural hyperplasia, and Merkel cell hyperplasia may not have a significant effect on treatment response.

The follicle-sinus complex of the bottlenose dolphin (Tursiops truncatus). Functional anatomy and possible evolutional significance of its somato-sensory innervation.

Vibrissae are tactile hairs found mainly on the rostrum of most mammals. The follicle, which is surrounded by a large venous sinus, is called "follicle-sinus complex" (FSC). This complex is highly innervated by somatosensitive fibers and reached by visceromotor fibers that innervate the surrounding vessels. The surrounding striated muscles receive somatomotor fibers from the facial nerve. The bottlenose dolphin (Tursiops truncatus), a frequently described member of the delphinid family, possesses this organ only in the postnatal period. However, information on the function of the vibrissal complex in this latter species is scarce. Recently, psychophysical experiments on the river-living Guiana dolphin (Sotalia guianensis) revealed that the FSC could work as an electroreceptor in murky waters. In the present study, we analyzed the morphology and innervation of the FSC of newborn (n=8) and adult (n=3) bottlenose dolphins. We used Masson's trichrome stain and antibodies against neurofilament 200kDa (NF 200), protein gene product (PGP 9.5), substance P (SP), calcitonin gene-related peptide, and tyrosine hydroxylase (TH) to characterize the FSC of the two age classes. Masson's trichrome staining revealed a structure almost identical to that of terrestrial mammals except for the fact that the FSC was occupied only by a venous sinus and that the vibrissal shaft lied within the follicle. Immunostaining for PGP 9.5 and NF 200 showed somatosensory fibers finishing high along the follicle with Merkel nerve endings and free nerve endings. We also found SP-positive fibers mostly in the surrounding blood vessels and TH both in the vessels and in the mesenchymal sheath. The FSC of the bottlenose dolphin, therefore, possesses a rich somatomotor innervation and a set of peptidergic visceromotor fibers. This anatomical disposition suggests a mechanoreceptor function in the newborns, possibly finalized to search for the opening of the mother's nipples. In the adult, however, this structure could change into a proprioceptive function in which the vibrissal shaft could provide information on the degree of rotation of the head. In the absence of psychophysical experiments in this species, the hypothesis of electroreception cannot be rejected.

Modelling the effects of age-related morphological and mechanical skin changes on the stimulation of tactile mechanoreceptors

Our sense of fine touch deteriorates as we age, a phenomenon typically associated with neurological changes to the skin. However, geometric and material changes to the skin may also play an important role on tactile perception and have not been studied in detail. Here, a finite element model is utilised to assess the extent to which age-related structural changes to the skin influence the tactile stimuli experienced by the mechanoreceptors. A numerical, hyperelastic, four-layered skin model was developed to simulate sliding of the finger against a rigid surface. The strain, deviatoric stress and strain energy density were recorded at the sites of the Merkel and Meissner receptors, whilst parameters of the model were systematically varied to simulate age-related geometric and material skin changes. The simulations comprise changes in skin layer stiffness, flattening of the dermal-epidermal junction and thinning of the dermis. It was found that the stiffness of the skin layers has a substantial effect on the stimulus magnitudes recorded at mechanoreceptors. Additionally, reducing the thickness of the dermis has a substantial effect on the Merkel disc whilst the Meissner corpuscle is particularly affected by flattening of the dermal epidermal junction. In order to represent aged skin, a model comprising a combination of ageing manifestations revealed a decrease in stimulus magnitudes at both mechanoreceptor sites. The result from the combined model differed from the sum of effects of the individually tested ageing manifestations, indicating that the individual effects of ageing cannot be linearly superimposed. Each manifestation of ageing results in a decreased stimulation intensity at the Meissner Corpuscle site, suggesting that ageing reduces the proportion of stimuli meeting the receptor amplitude detection threshold. This model therefore offers an additional biomechanical explanation for tactile perceptive degradation amongst the elderly. Applications of the developed model are in the evaluation of cosmetics products aimed at mitigating the effects of ageing, e.g. through skin hydration and administration of antioxidants, as well as in the design of products with improved tactile sensation, e.g. through the optimisation of materials and surface textures.

A flexible artificial intrinsic-synaptic tactile sensory organ

Imbuing bio-inspired sensory devices with intelligent functions of human sensory organs has been limited by challenges in emulating the preprocessing abilities of sensory organs such as reception, filtering, adaptation, and sensory memory at the device level itself. Merkel cells, which is a part of tactile sensory organs, form synapse-like connections with afferent neuron terminals referred to as Merkel cell-neurite complexes. Here, inspired by structure and intelligent functions of Merkel cell-neurite complexes, we report a flexible, artificial, intrinsic-synaptic tactile sensory organ that mimics synapse-like connections using an organic synaptic transistor with ferroelectric nanocomposite gate dielectric of barium titanate nanoparticles and poly(vinylidene fluoride-trifluoroethylene). Modulation of the post-synaptic current of the device induced by ferroelectric dipole switching due to triboelectric-capacitive coupling under finger touch allowed reception and slow adaptation. Modulation of synaptic weight by varying the nanocomposite composition of gate dielectric layer enabled tuning of filtering and sensory memory functions.