Meissner Corpuscles Research Articles

Investigating mechanoreceptor variability and morphometric proxies in Rhesus Macaques: Implications for primate precision touch studies.

The origin of primates has long been associated with an increased emphasis on manual grasping and touch. Precision touch, facilitated by specialized mechanoreceptors in glabrous skin, provides critical sensory feedback for grasping-related tasks and perception of ecologically-relevant stimuli. Despite its importance, studies of mechanoreceptors in primate hands are limited, in part due to challenges of sample availability and histological methods. Dermatoglyphs have been proposed as alternative proxies of mechanoreceptor density. We investigated the relationships between mechanoreceptors (Meissner and Pacinian corpuscles), dermatoglyphs, and demography in the apical finger pads of 15 juvenile to adult rhesus macaques (Macaca mulatta) from a free-ranging population at Cayo Santiago Primate Field Station (Puerto Rico). Our results indicate substantial interindividual variation in mechanoreceptor density (Meissner corpuscles: 11.9-43.3 corpuscles/mm2; Pacinian corpuscles: 0-4.5 corpuscles/mm2). While sex and digit were generally not associated with variation, there was strong evidence of a developmental effect. Specifically, apical pad length, Meissner corpuscle size, and Pacinian corpuscle depth increased while mechanoreceptor densities decreased throughout juvenescence, suggesting that primate mechanoreceptors change as fingers grow during adolescence and then stabilize at physical maturity. We also found Meissner corpuscle density was significantly associated with dermatoglyph ridge width and spacing, such that density predicted by a dermatoglyph model was strongly correlated with observed values. Dermatoglyphs thus offer a useful proxy of relative Meissner corpuscle density in primates, which opens exciting avenues of noninvasive research. Finally, our results underscore the importance of considering demographic factors and methodology in comparative studies of primate touch.

Postsurgical tactile-evoked pain: a role for brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent novel tactile corpuscles.

Millions of people undergo surgical procedures each year with many developing postsurgical pain. Dynamic allodynia can arise when, for example, clothing brushing close to the surgical site elicits pain. The allodynia circuits that enable crosstalk between afferent tactile inputs and central pain circuits have been studied, but the peripheral tactile drive has not been explored. Investigate the innervation of the skin in the rat plantar hindpaw skin-muscle incision model. Incision increased epidermal thickness and cell layers and reduced intraepidermal nerve fibre density, identified with PGP9.5 immunostaining. Strikingly, Collagen IV immunostaining revealed the development of dermal protrusions, oriented towards the incision site, that were reminiscent of the dermal papillae that exist in glabrous footpads. S100 immunostaining for lamellar Schwann cells revealed the presence of novel tactile corpuscles (S100-positive bulb) within incision-induced putative dermal papillae. The occurrence of these novel tactile corpuscles coincided with behavioural observations of dynamic allodynia. Tactile corpuscles require brain-derived neurotrophic factor- tropomyosin receptor kinase B (BDNF-TrkB) signalling to form during development, and an increase in BDNF-immunostaining intensity was observed close to the incision site. Local acute administration of TrkB-Fc, to block BDNF-TrkB signalling, reduced, by approximately 50%, both tactile corpuscle size (S100+ bulb area) and dynamic allodynia. Surgery induces the development of novel tactile corpuscles in the incision surround, in a BDNF-TrKB-dependent manner, that contributes to postsurgical tactile-evoked pain.

Piezo2 voltage-block regulates mechanical pain sensitivity.

PIEZO2 is a trimeric mechanically-gated ion channel expressed by most sensory neurons in the dorsal root ganglia. Mechanosensitive PIEZO2 channels are also genetically required for normal touch sensation in both mice and humans. We previously showed that PIEZO2 channels are also strongly modulated by membrane voltage. Specifically, it is only at very positive voltages that all channels are available for opening by mechanical force. Conversely, most PIEZO2 channels are blocked at normal negative resting membrane potentials. The physiological function of this unusual biophysical property of PIEZO2 channels, however, remained unknown. We characterized the biophysical properties of three PIEZO2 ion channel mutations at an evolutionarily conserved arginine (R2756). Using genome engineering in mice we generated Piezo2R2756H/R2756H and Piezo2R2756K/R2756K knock-in mice to characterize the physiological consequences of altering PIEZO2 voltage sensitivity in vivo. We measured endogenous mechanosensitive currents in sensory neurons isolated from the dorsal root ganglia and characterized mechanoreceptor and nociceptor function using electrophysiology. Mice were also assessed behaviourally and morphologically. Mutations at the conserved Arginine (R2756) dramatically changed the biophysical properties of the channel relieving voltage block and lowering mechanical thresholds for channel activation. Piezo2R2756H/R2756H and Piezo2R2756K/R2756K knock-in mice that were homozygous for gain-of-function mutations were viable and were tested for sensory changes. Surprisingly, mechanosensitive currents in nociceptors, neurons that detect noxious mechanical stimuli, were substantially sensitized in Piezo2 knock-in mice, but mechanosensitive currents in most mechanoreceptors that underlie touch sensation were only mildly affected by the same mutations. Single-unit electrophysiological recordings from sensory neurons innervating the glabrous skin revealed that rapidly-adapting mechanoreceptors that innervate Meissner's corpuscles exhibited slightly decreased mechanical thresholds in Piezo2 knock-in mice. Consistent with measurements of mechanically activated currents in isolated sensory neurons essentially all cutaneous nociceptors, both fast conducting Aδ-mechanonociceptors and unmyelinated C-fibre nociceptors were substantially more sensitive to mechanical stimuli and indeed acquired receptor properties similar to ultrasensitive touch receptors in Piezo2 knock-in mice. Mechanical stimuli also induced enhanced ongoing activity in cutaneous nociceptors in Piezo2 knock-in mice and hyper-sensitive PIEZO2 channels were sufficient alone to drive ongoing activity, even in isolated nociceptive neurons. Consistently, Piezo2 knock-in mice showed substantial behavioural hypersensitivity to noxious mechanical stimuli. Our data indicate that ongoing activity and sensitization of nociceptors, phenomena commonly found in human chronic pain syndromes, can be driven by relieving the voltage-block of PIEZO2 ion channels. Indeed, membrane depolarization caused by multiple noxious stimuli may sensitize nociceptors by relieving voltage-block of PIEZO2 channels.

Role of Piezo2 in Schwann Cell Volume Regulation and Its Impact on Neurotrophic Release Regulation.

Tactile perception relies on mechanoreceptors and nerve fibers, including c-fibers, Aβ-fibers and Aδ-fibers. Schwann cells (SCs) play a crucial role in supporting nerve fibers, with non-myelinating SCs enwrapping c-fibers and myelinating SCs ensheathing Aβ and Aδ fibers. Recent research has unveiled new functions for cutaneous sensory SCs, highlighting the involvement of nociceptive SCs in pain perception and Meissner corpuscle SCs in tactile sensation. Furthermore, Piezo2, previously associated with Merkel cell tactile sensitivity, has been identified in SCs. The goal of this study was to investigate the channels implicated in SC mechanosensitivity and the release process of neurotrophic factor secretion. Immortalized IFRS1 SCs and human primary SCs generated two distinct subtypes of SCs: undifferentiated and differentiated SCs. Quantitative PCR was employed to evaluate the expression of differentiation markers and mechanosensitive channels, including TRP channels (TRPV4, TRPM7 and TRPA1) and Piezo channels (Piezo1 and Piezo2). To validate the functionality of specific mechanosensitive channels, Ca2+ imaging and electronic cell sizing experiments were conducted under hypotonic conditions, and inhibitors and siRNAs were used. Protein expression was assessed by Western blotting and immunostaining. Additionally, secretome analysis was performed to evaluate the release of neurotrophic factors in response to hypotonic stimulation, with BDNF, a representative trophic factor, quantified using ELISA. Induction of differentiation increased Piezo2 mRNA expression levels both in IFRS1 and in human primary SCs. Both cell types were responsive to hypotonic solutions, with differentiated SCs displaying a more pronounced response. Gd3+ and FM1-43 effectively inhibited hypotonicity-induced Ca2+ transients in differentiated SCs, implicating Piezo2 channels. Conversely, inhibitors of Piezo1 and TRPM7 (Dooku1 and NS8593, respectively) had no discernible impact. Moreover, Piezo2 in differentiated SCs appeared to participate in regulatory volume decreases (RVD) after cell swelling induced by hypotonic stimulation. A Piezo2 deficiency correlated with reduced RVD and prolonged cell swelling, leading to heightened release of the neurotrophic factor BDNF by upregulating the function of endogenously expressed Ca2+-permeable TRPV4. Our study unveils the mechanosensitivity of SCs and implicates Piezo2 channels in the release of neurotrophic factors from SCs. These results suggest that Piezo2 may contribute to RVD, thereby maintaining cellular homeostasis, and may also serve as a negative regulator of neurotrophic factor release. These findings underscore the need for further investigation into the role of Piezo2 in SC function and neurotrophic regulation.

Skin keratinocyte-derived SIRT1 and BDNF modulate mechanical allodynia in mouse models of diabetic neuropathy.

Diabetic neuropathy is a debilitating disorder characterized by spontaneous and mechanical allodynia. The role of skin mechanoreceptors in the development of mechanical allodynia is unclear. We discovered that mice with diabetic neuropathy had decreased sirtuin 1 (SIRT1) deacetylase activity in foot skin, leading to reduced expression of brain-derived neurotrophic factor (BDNF) and subsequent loss of innervation in Meissner corpuscles, a mechanoreceptor expressing the BDNF receptor TrkB. When SIRT1 was depleted from skin, the mechanical allodynia worsened in diabetic neuropathy mice, likely due to retrograde degeneration of the Meissner-corpuscle innervating Aβ axons and aberrant formation of Meissner corpuscles which may have increased the mechanosensitivity. The same phenomenon was also noted in skin-keratinocyte specific BDNF knockout mice. Furthermore, overexpression of SIRT1 in skin induced Meissner corpuscle reinnervation and regeneration, resulting in significant improvement of diabetic mechanical allodynia. Overall, the findings suggested that skin-derived SIRT1 and BDNF function in the same pathway in skin sensory apparatus regeneration and highlighted the potential of developing topical SIRT1-activating compounds as a novel treatment for diabetic mechanical allodynia.

Foreskin neurovascular structure: A histological analysis comparing 0–3 years and 6–11 years children

Circumcision is a surgical operation that is frequently performed throughout the world due to religious, cultural, and medical reasons. The best age for circumcision is still debatable, with different procedures depending on geography, culture, and surgeon preference. This study aims to immunohistochemical examination using S100 staining and histologically evaluate the neurovascular structures in foreskin samples obtained from children aged 0-3 years and 6-11 years. The goal is to provide guidance in determining an appropriate age for circumcision based on these data. Concerns regarding potential effects on glans sensitivity and sexual function led to the investigation and comparison of sensory innervation in the foreskin of children aged 0-3 and 6-11 years, a total 54 samples, divided into pre-phallic (0-3 years) and post-phallic (6-11 years) groups, were examined. The mean number of Meissner and Pacinian corpuscles, Ruffini endings, free nerve endings and the diameters of arteries were investigated. Our findings show that compared to the 6-11 age group, the 0-3 age group had considerably lower sensory innervation in terms of, Meissner's corpuscles, Pacinian corpuscles, Ruffini endings and free nerve endings. Additionally, the diameter of arteries was noticeably smaller in the 0-3 age group. In conclusion, this study supports the idea that circumcision performed in the early years of life may be associated with less adverse effects on neurovascular structures.

Evolution of snake skin: Role of cutaneous tactile corpuscles in Hierophis viridiflavus (Lacépède, 1789)

AbstractThe skin of snakes acts as the first interface between these reptiles and the environment they live in. It plays an important role in the ecology of these organisms, and specialised structures, such as tactile corpuscles, are crucial in the sensing of a wide variety of stimuli. This study, by examining the presence, localisation and colocalisation of serotonin, substance P, PGP 9.5 and tubulin, wants to demonstrate the sensory role that these structures play in the ecology of the Green whip snake Hierophis viridiflavus (Lacépède, 1789). This study presents the first evaluation of nerve and immune molecules (TLR2) in the tactile corpuscles of H. viridiflavius ventral skin, indicating a potential defence role of these structures. These findings provide valuable information on the ecology of snakes, their defence systems, and their evolutionary morphostructural adaptations. Additionally, the identification of these corpuscles could provide valuable support for taxonomic recognition. Furthermore, this study expands the knowledge about stimuli sensing in snakes.

Bilateral deficiency of Meissner corpuscles and papillary microvessels in patients with acute complex regional pain syndrome.

Complex regional pain syndrome (CRPS) presents postinjury with disproportionate pain and neuropathic, autonomic, motor symptoms, and skin texture affection. However, the origin of these multiplex changes is unclear. Skin biopsies offer a window to analyze the somatosensory and vascular system as well as skin trophicity with their protecting barriers. In previous studies, barrier-protective exosomal microRNAs were altered in CRPS. We here postulated that tissue architecture and barrier proteins are already altered at the beginning of CRPS. We analyzed ipsilateral and contralateral skin biopsies of 20 fully phenotyped early CRPS patients compared with 20 age- and sex-matched healthy controls. We established several automated unbiased methods to comprehensively analyze microvessels and somatosensory receptors as well as barrier proteins, including claudin-1, claudin-5, and claudin-19. Meissner corpuscles in the skin were bilaterally reduced in acute CRPS patients with some of them lacking these completely. The number of Merkel cells and the intraepidermal nerve fiber density were not different between the groups. Dermal papillary microvessels were bilaterally less abundant in CRPS, especially in patients with allodynia. Barrier proteins in keratinocytes, perineurium of dermal nerves, Schwann cells, and papillary microvessels were not affected in early CRPS. Bilateral changes in the tissue architecture in early CRPS might indicate a predisposition for CRPS that manifests after injury. Further studies should evaluate whether these changes might be used to identify risk patients for CRPS after trauma and as biomarkers for outcome.

Skin innervation across amyotrophic lateral sclerosis clinical stages: new prognostic biomarkers.

Over recent decades, peripheral sensory abnormalities, including the evidence of cutaneous denervation, have been reported among the non-motor manifestations in amyotrophic lateral sclerosis (ALS). However, a correlation between cutaneous innervation and clinical features has not been found. The aims of this study were to assess sensory involvement by applying a morpho-functional approach to a large population of ALS patients stratified according to King's stages and correlate these findings with the severity and prognosis of the disease. We recruited 149 ALS patients and 41 healthy controls. Patients undertook clinical questionnaires for small fibre neuropathy symptoms (Small Fiber Neuropathy Symptoms Inventory Questionnaire) and underwent nerve conductions studies (NCS) and 3-mm punch skin biopsies from leg, thigh and fingertip. We assessed intraepidermal nerve fibre (IENF) and Meissner corpuscle (MC) density by applying an indirect immunofluorescence technique. Moreover, a subset of 65 ALS patients underwent a longitudinal study with repeat biopsies from the thigh at 6- and 12-month follow-ups. Serum NfL levels were measured in 40 patients. Sensory symptoms and sensory NCS abnormalities were present in 32.2% and 24% of patients, respectively, and increased across clinical stages. Analogously, we observed a progressive reduction in amplitude of the sensory and motor ulnar nerve potential from stage 1 to stage 4. Skin biopsy showed a significant loss of IENFs and MCs in ALS compared with healthy controls (all P < 0.001). Across the clinical stages, we found a progressive reduction in MCs (P = 0.004) and an increase in IENFs (all P < 0.027). The increase in IENFs was confirmed by the longitudinal study. Interestingly, the MC density inversely correlated with NfL level (r = -0.424, P = 0.012), and survival analysis revealed that low MC density, higher NfL levels and increasing IENF density over time were associated with a poorer prognosis (all P < 0.024). To summarize, in patients with ALS, peripheral sensory involvement worsens in parallel with motor disability. Furthermore, the correlation between skin innervation and disease activity may suggest the use of skin innervation as a putative prognostic biomarker.

Immunohistochemical detection of PIEZO1 and PIEZO2 in human digital Meissner´s corpuscles

BackgroundThe cutaneous end organ complexes or cutaneous sensory corpuscles are specialized sensory organs associated to low-threshold mechanoreceptors. Mechano-gated proteins forming a part of ion channels have been detected in both the axon and terminal glial cells of Meissner corpuscles, a specific cutaneous end organ complex in the human glabrous skin. The main candidates to mechanotransduction in Meissner corpuscles are members of the Piezo family of cationic ion channels. PIEZO2 has been detected in the axon of these sensory structures whereas no data exists about the occurrence and cell localization of PIEZO1. MethodsSkin samples (n = 18) from the palmar aspect of the distal phalanx of the first and second fingers were analysed (8 female and 10 males; age range 26 to 61 26–61 years). Double immunofluorescence for PIEZO1 and PIEZO2 together with axonal or terminal glial cell markers was captured by laser confocal microscopy, and the percentage of PIEZOs positive Meissner corpuscles was evaluated. ResultsMCs from human fingers showed variable morphology and degree of lobulation. Regarding the basic immunohistochemical profile, in all cases the axons were immunoreactive for neurofilament proteins, neuron specific enolase and synaptophysin, while the lamellar cells displayed strong S100P immunoreactivity. PIEZO1 was detected co-localizing with axonal markers, but never with terminal glial cell markers, in the 56% of Meissner corpuscles; weak but specific immunofluorescence was additionally detected in the epidermis, especially in basal keratinocytes. Similarly, PIEZO2 immunoreactivity was found restricted to the axon in the 85% of Meissner corpuscles. PIEZO2 positive Merkel cells were also regularly found. ConclusionsPIEZO1 and PIEZO2 are expressed exclusively in the axon of a subpopulation of human digital Meissner corpuscles, thus suggesting that not only PIEZO2, but also PIEZO1 may be involved in the mechanotransduction from low-threshold mechanoreceptors.

Fully‐Printed Bionic Tactile E‐Skin with Coupling Enhancement Effect to Recognize Object Assisted by Machine Learning

AbstractIn the pursuit of tactile sensation resembling human skin, the electronic skin (E‐skin) has long been a subject of interest and inspires the exploration of various biomimetic structures. Nevertheless, the exceptional functionality of living organisms arises from the synergistic interplay of multiple internal factors, i.e. the coupling enhancement effect, which has received limited attention in existing studies. Here, a tactile E‐skin featuring a multicoupled biomimetic structure that mimics three coupling elements found in the skin: Stratum spinosum, Meissner corpuscle, and Piezo2 protein, is proposed. By amalgamating their distinguishing characteristics, this bionic E‐skin surpasses the performance of conventional counterparts such as sensitivity as high as 388.5 kPa−1, hysteresis as low as 0.76%, and response times as short as 10 ms. Furthermore, its fabrication methodology of efficient 3D printing shows great advantages in terms of production cost and customization. Finally, the sensor is expanded to a 9 × 9 pixels array for a machine learning‐assisted intellisense system to recognize the fruits as a human does, achieving an accuracy of 91.4%. All of these prove the promising potential of this multicoupled biomimetic structure in wearable electronics, human–machine interface, soft robotics, and artificial sensing.

Skin-type-dependent development of murine mechanosensory neurons.

Mechanosensory neurons innervating the skin underlie our sense of touch. Fast-conducting, rapidly adapting mechanoreceptors innervating glabrous (non-hairy) skin form Meissner corpuscles, while in hairy skin, they associate with hair follicles, forming longitudinal lanceolate endings. How mechanoreceptors develop axonal endings appropriate for their skin targets is unknown. We report that mechanoreceptor morphologies across different skin regions are indistinguishable during early development but diverge post-natally, in parallel with skin maturation. Neurons terminating along the glabrous and hairy skin border exhibit hybrid morphologies, forming both Meissner corpuscles and lanceolate endings. Additionally, molecular profiles of neonatal glabrous and hairy skin-innervating neurons largely overlap. In mouse mutants with ectopic glabrous skin, mechanosensory neurons form end-organs appropriate for the altered skin type. Finally, BMP5 and BMP7 are enriched in glabrous skin, and signaling through type I bone morphogenetic protein (BMP) receptors in neurons is critical for Meissner corpuscle morphology. Thus, mechanoreceptor morphogenesis is flexibly instructed by target tissues.

The good, the bald, and the hairy: A mechanosensor meets its fate at the target.

In this issue of Developmental Cell, Koutsioumpa etal. (2023) investigate the maturation of low-threshold mechanoreceptor nerve endings in both hairy and glabrous skin types and discover a critical role for target-derived BMP in the development of Meissner corpuscles in glabrous (i.e., hairless) skin.

Exploring somatosensory innervation of the human lip: A focus on the vermilion

BackgroundThe lips are a vital component of the face and are densely innervated to perform various functions. The lip edges are covered with mucocutaneous tissue called vermilion which is particularly receptive to touch and temperature. The aim of this study was to investigate the somatosensory innervation of human lips, focusing on sensory corpuscles and the presence of mechano-gated (ASIC2, PIEZO2, and TRPV4) and thermosensing (TRPV1, TRPM2, and RPM8) ion channels within them. MethodsTwelve intact lips (6 upper and 6 lower) were obtained from non-embalmed frozen cadavers (five females and seven males) with an age range of 60–80 years. The specimens were divided into three zones (medial, lateral, and median). The morphotypes of sensory corpuscles and their immunohistochemical profile was analysed. The occurrence of ion channels involved in mechanosensation and temperature detection was examined using various antibodies. Sensory corpuscle density was quantified in vermilion sections, and statistical analyses were conducted to assess differences between the upper and lower lips, as well as between females and males (p < 0.05). ResultsDifferent morphotypes of sensory corpuscles were identified: Ruffini-like associated with hair follicles, Meissner and glomerular corpuscles in the vermilion, and less classifiable sensory corpuscles within the mucosa. The density of sensory corpuscles in the vermilion was higher in the upper lip than in the lower lip; glomerular corpuscles predominated in the medial and median segments, whereas Meissner corpuscles were more abundant in the lateral segment. No sex-related differences were observed in the density or distribution of the two main corpuscular morphotypes. In contrast, the axons of both the glomeruli and Meissner corpuscles regularly displayed ASIC2 and PIEZO2 immunoreactivity, whereas immunoreactivity for TRPV1, TRPV4, TRPM2, and TRPV8 was absent. ConclusionsThese results demonstrate that the sensory corpuscles of the vermilion are a mixture of those typical of glabrous skin mucocutaneous tissues. The presence of PIEZO2 and ASIC2 in their axons suggests that these sensory corpuscles function as mechanosensors.

Tactile Recognition of Shape and Texture on the Same Substrate

Due to the difficulties in designing sensor arrays with a wide detection range, high sensitivity, and the sensing ability to convert tangential force into normal force on the same substrate, the integration of shape and texture recognitions in one electronic skin (e‐skin) has not been realized so far. Herein, an e‐skin tactile‐sensing system is presented, based on resistive pressure‐sensing units (serving as Meissner corpuscles) unevenly distributed on a bionic hand‐shaped polyimide substrate, which can realize shape and texture recognitions concurrently. A multilayer microporous structure with different pores is designed and introduced into the sensor, which enables each sensing unit ultrahigh sensitivity and a wide detection range. Meanwhile, a customized micro‐pyramid array is developed and assembled to the sensor array, which realizes the transformation from tangential force to normal force. With the help of artificial intelligence technology, the recognition accuracy reaches 100% for 8 different shapes, and 99.7% for 10 different textures, respectively. The proposed design strategy enables compatible fabrication, simple signal processing, and convenient extension of bionic free‐shaped e‐skin, which paves a promising way for the popularization of e‐skin in large‐scale intelligent wearable fields.

Bovine Meissner-like corpuscle and evolutionary ecology of mammalian somatosensory acuity.

The mammalian snout has Meissner's corpuscles (MCs), which transmit epicritic sensations as the animal explores its surroundings. To comprehend the somatosensory acuity in mammals, we examined the structural organization and density of bovine Meissner-like corpuscles (BMLCs) at various ages and compared the changes with other mammalian MCs. The skin from the snout of cows or oxen (2-11 years old) was obtained and processed through routine histological technique. Five-μm thick sections were prepared, silver stained according to the Bielschowsky technique as modified by Winkelman and Schmidt (Mayo Clinic Proceedings, 1957, 217), and observed under a compound light microscope quantitatively and qualitatively. The glabrous skin of the cow snout consisted of two types of BMLCs: One was a cylindrical or elongated structure found in the dermal papillae. The other type was spherical and developed in the superficial layers of the epidermis. BMLCs consisted of both coarse and fine nerve fibres. In the young, the corpuscle comprised thin nerve fibres with indistinct cell outlines. In adults, nerve fibres in the corpuscles were closely packed, and networks, varicosities and end bulbs were well developed. With advancing age, the MCs attenuated into a disorganized mass of nerve fibres. The bovine snout is a highly evolved somatosensory organ due to its rich nerve supply and functionally resembles the anthropoid fingertip. Somatosensory acuity will be lower in the glabrous bovine skin than in primate glabrous skin of the fingertip, as the nerve terminals within the BMLCs are less elaborate in content and structural complexity.

Three-dimensional reconstructions of mechanosensory end organs suggest a unifying mechanism underlying dynamic, light touch

Across mammalian skin, structurally complex and diverse mechanosensory end organs respond to mechanical stimuli and enable our perception of dynamic, light touch. How forces act on morphologically dissimilar mechanosensory end organs of the skin to gate the requisite mechanotransduction channel Piezo2 and excite mechanosensory neurons is not understood. Here, we report high-resolution reconstructions of the hair follicle lanceolate complex, Meissner corpuscle, and Pacinian corpuscle and the subcellular distribution of Piezo2 within them. Across all three end organs, Piezo2 is restricted to the sensory axon membrane, including axon protrusions that extend from the axon body. These protrusions, which are numerous and elaborate extensively within the end organs, tether the axon to resident non-neuronal cells via adherens junctions. These findings support a unified model for dynamic touch in which mechanical stimuli stretch hundreds to thousands of axon protrusions across an end organ, opening proximal, axonal Piezo2 channels and exciting the neuron.

3D architecture and a bicellular mechanism of touch detection in mechanosensory corpuscle.

Mechanosensory corpuscles detect transient touch and vibration in the skin of vertebrates, enabling precise sensation of the physical environment. The corpuscle contains a mechanoreceptor afferent surrounded by lamellar cells (LCs), but corpuscular ultrastructure and the role of LCs in touch detection are unknown. We report the three-dimensional architecture of the avian Meissner (Grandry) corpuscle acquired using enhanced focused ion beam scanning electron microscopy and machine learning-based segmentation. The corpuscle comprises a stack of LCs interdigitated with terminal endings from two afferents. Simultaneous electrophysiological recordings from both cell types revealed that mechanosensitive LCs use calcium influx to trigger action potentials in the afferent and thus serve as physiological touch sensors in the skin. The elaborate architecture and bicellular sensory mechanism in the corpuscles, which comprises the afferents and LCs, create the capacity for nuanced encoding of the submodalities of touch.

Correlations among Firing Rates of Tactile, Thermal, Gustatory, Olfactory, and Auditory Sensations Mimicked by Artificial Hybrid Fluid (HF) Rubber Mechanoreceptors

In order to advance the development of sensors fabricated with monofunctional sensation systems capable of a versatile response to tactile, thermal, gustatory, olfactory, and auditory sensations, mechanoreceptors fabricated as a single platform with an electric circuit require investigation. In addition, it is essential to resolve the complicated structure of the sensor. In order to realize the single platform, our proposed hybrid fluid (HF) rubber mechanoreceptors of free nerve endings, Merkel cells, Krause end bulbs, Meissner corpuscles, Ruffini endings, and Pacinian corpuscles mimicking the bio-inspired five senses are useful enough to facilitate the fabrication process for the resolution of the complicated structure. This study used electrochemical impedance spectroscopy (EIS) to elucidate the intrinsic structure of the single platform and the physical mechanisms of the firing rate such as slow adaption (SA) and fast adaption (FA), which were induced from the structure and involved the capacitance, inductance, reactance, etc. of the HF rubber mechanoreceptors. In addition, the relations among the firing rates of the various sensations were clarified. The adaption of the firing rate in the thermal sensation is the opposite of that in the tactile sensation. The firing rates in the gustation, olfaction, and auditory sensations at frequencies of less than 1 kHz have the same adaption as in the tactile sensation. The present findings are useful not only in the field of neurophysiology, to research the biochemical reactions of neurons and brain perceptions of stimuli, but also in the field of sensors, to advance salient developments in sensors mimicking bio-inspired sensations.

Skin-dependent morphological and molecular maturation of specialized mechanosensory neurons (S34.005)

<h3>Objective:</h3> Identification of the developmental steps leading to somatosensory neuron development. <h3>Background:</h3> Our sense of touch is essential for life and relies on Low-Threshold Mechanoreceptors (LTMRs). LTMR subtypes characterized by early embryonic expression of Ntrk2 (TrkB) and Ret exhibit distinct properties depending on the skin region they innervate - hairy skin or glabrous(hairless) skin. In glabrous skin, TrkB+ and Ret+ LTMRs form Meissner corpuscles, while in hairy skin they form longitudinal lanceolate endings around hair follicles. These morphological features reflect the physiological properties and specialized functions of these neurons. The developmental steps leading to glabrous and hairy skin LTMR properties are largely unknown, in particular whether they are genetically pre-specified or whether interactions with different target skin regions define their unique features. <h3>Design/Methods:</h3> Sparse genetic labeling experiments demonstrate that morphological specialization of glabrous- and hairy paw skin-innervating TrkB+ and Ret+ LTMRs arise at nearly identical times during postnatal development. Interestingly, we find that individual neurons that terminate along the border of glabrous and hairy skin, termed “border neurons”, exhibit branches that form both lanceolate endings and Meissner corpuscle endings. Additionally, transcriptomic profiling and RNAscope experiments show that neonatal glabrous skin-and hairy skin-innervating TrkB+ and Ret+ neurons are transcriptionally similar, although distinct from other DRG neuron types. Lastly, using mouse mutants that have either ectopic glabrous skin or ectopic hairy skin we find that neurons that innervate ectopic skin regions of these mutants form ending types (either lanceolate or Meissner corpuscle endings) in accordance with the ectopic skin type. <h3>Results:</h3> These findings support a model in which embryonic TrkB+ and Ret+ LTMRs are able to form either Meissner corpuscle or lanceolate endings, and that the skin target region differentially instructs morphological maturation of these LTMR types. <h3>Conclusions:</h3> This model implies that neuronal identity in the peripheral nervous system is flexibly determined by target tissue. <b>Disclosure:</b> Dr. Koutsioumpa has nothing to disclose. Dr. Santiago has nothing to disclose. Miss Jacobs has nothing to disclose. Dr. Lehnert has received personal compensation for serving as an employee of Flagship Pioneering. Dr. Ginty has nothing to disclose.