Fingerprint lines may not directly affect SA-I mechanoreceptor response

Understanding how skin microstructure affects slowly adapting type I (SA-I) mechanoreceptors in encoding edge discontinuities is fundamental to understanding our sense of touch. Skin microstructure, in particular papillary ridges, has been thought to contribute to edge and gap sensation. Cauna's 1954 model of touch sensibility describes a functional relationship between papillary ridges and edge sensation. His lever arm model proposes that the papillary ridge (exterior fingerprint line) and underlying intermediate ridge operate as a single unit, with the intermediate ridge acting as a lever which magnifies indentation imposed at the papillary ridge. This paper contests the validity of the lever arm model. While correctly representing the anatomy, this mechanism inaccurately characterizes the function of the papillary ridges. Finite element analysis and assessment of the critical anatomy indicate that papillary ridges have little direct effect on how SA-I receptors respond to the indentation of static edges. Our analysis supports a revised (stiff shell-elastic bending support) interpretation where the epidermis is split into two major layers with a stiff, deformable shell over an elastic bending support. Recent physiological, electrophysiological, and psychophysical findings support our conclusion that the function of the intermediate ridge is distinct from the function of the papillary ridge.     

3-D finite-element models of human and monkey fingertips to investigate the mechanics of tactile sense

The biomechanics of skin and underlying tissues plays a fundamental role in the human sense of touch. It governs the mechanics of contact between the skin and an object, the transmission of the mechanical signals through the skin, and their transduction into neural signals by the mechanoreceptors. To better understand the mechanics of touch, it is necessary to establish quantitative relationships between the loads imposed on the skin by an object, the state of stresses/strains at mechanoreceptor locations, and the resulting neural response. Towards this goal, 3-D finite-element models of human and monkey fingertips with realistic external geometries were developed. By computing fingertip model deformations under line loads, it was shown that a multi-layered model was necessary to match previously obtained in vivo data on skin surface displacements. An optimal ratio of elastic moduli of the layers was determined through numerical experiments whose results were matched with empirical data. Numerical values of the elastic moduli of the skin layers were obtained by matching computed results with empirically determined force-displacement relationships for a variety of indentors. Finally, as an example of the relevance of the model to the study of tactile neural response, the multilayered 3-D finite-element model was shown to be able to predict the responses of the slowly adapting type I (SA-I) mechanoreceptors to indentations by complex object shapes.     

Localization of Merkel cells in the monkey skin: an anatomical model

The Merkel cell-neurite complex is considered to be one class of mechanoreceptors in the skin. Merkel cells are innervated by slowly adapting type I (SAI) tactile nerve fibers. In this paper, the detailed distribution of Merkel cells is studied by immunohistochemical labeling of the monkey (Macaca fascicularis) digital glabrous skin. Specific morphometric variables (density of intermediate epidermal ridges and Merkel cells, distance between skin surface and ridge tips and bases, maximum and average cell counts per ridge, distance between cells and ridges) were measured by a combination of light/fluorescence microscopy and computer-image analysis. The morphometric results were similar for each digit of the monkey's hand. Next, the anatomical data were used to form a three-dimensional reconstruction of the Merkel-cell distribution in the fingertip skin. A patch of the distal-pad surface was then computationally flattened to obtain the two-dimensional distribution of Merkel cells. Based on previous anatomical and physiological data, SAI fibers were simulated to innervate clusters of Merkel cells in the distal-pad surface. On average, 28 cells were innervated by a single fiber. The resulting anatomical model may be used to estimate the population response of SAI fibers by incorporating spike generation.     

Multiscale Mechanical Model of the Pacinian Corpuscle Shows Depth and Anisotropy Contribute to the Receptor’s Characteristic Response to Indentation

Cutaneous mechanoreceptors transduce different tactile stimuli into neural signals that produce distinct sensations of touch. The Pacinian corpuscle (PC), a cutaneous mechanoreceptor located deep within the dermis of the skin, detects high frequency vibrations that occur within its large receptive field. The PC is comprised of lamellae that surround the nerve fiber at its core. We hypothesized that a layered, anisotropic structure, embedded deep within the skin, would produce the nonlinear strain transmission and low spatial sensitivity characteristic of the PC. A multiscale finite-element model was used to model the equilibrium response of the PC to indentation. The first simulation considered an isolated PC with fiber networks aligned with the PC’s surface. The PC was subjected to a 10 μm indentation by a 250 μm diameter indenter. The multiscale model captured the nonlinear strain transmission through the PC, predicting decreased compressive strain with proximity to the receptor’s core, as seen experimentally by others. The second set of simulations considered a single PC embedded epidermally (shallow) or dermally (deep) to model the PC’s location within the skin. The embedded models were subjected to 10 μm indentations at a series of locations on the surface of the skin. Strain along the long axis of the PC was calculated after indentation to simulate stretch along the nerve fiber at the center of the PC. Receptive fields for the epidermis and dermis models were constructed by mapping the long-axis strain after indentation at each point on the surface of the skin mesh. The dermis model resulted in a larger receptive field, as the calculated strain showed less indenter location dependence than in the epidermis model.     

Rendering edge enhancement tactile phenomenon by friction variation in dynamic touch

Variable friction tactile displays have been recently used to render virtual textures and gratings. Neural basis of perceptual mechanism of detection of edge-like features resulting in discrimination of virtual gratings during active touching these tactile actuators is studied using a finite-element biomechanical model of human fingertip. The predicted neural response of the mechanoreceptors, i.e. the computed strain energy density at the location of selected mechanoreceptors as a measure of neural discharge rate of the corresponding receptors, to local reduction of friction between fingerpad and surface are shown to exhibit a similar shape as the edge enhancement phenomenon, particularly in a sudden burst at the boundary of variable friction regions. This phenomenon is supposed to account for the illusion of virtual edges rendered through the modification of contact forces. The presence of this sudden burst under varied model parameters was investigated. It was shown that while the appearance of this phenomenon in simulation results was invariant to model parameters, associated alteration of the edge enhancement ratio might be considered for the purpose of the tuning of the variable friction tactile display.     

Touch sense: Functional organization and molecular determinants of mechanosensitive receptors

Cutaneous mechanoreceptors are localized in the various layers of the skin where they detect a wide range of mechanical stimuli, including light brush, stretch, vibration and noxious pressure. This variety of stimuli is matched by a diverse array of specialized mechanoreceptors that respond to cutaneous deformation in a specific way and relay these stimuli to higher brain structures. Studies across mechanoreceptors and genetically tractable sensory nerve endings are beginning to uncover touch sensation mechanisms. Work in this field has provided researchers with a more thorough understanding of the circuit organization underlying the perception of touch. Novel ion channels have emerged as candidates for transduction molecules and properties of mechanically gated currents improved our understanding of the mechanisms of adaptation to tactile stimuli. This review highlights the progress made in characterizing functional properties of mechanoreceptors in hairy and glabrous skin and ion channels that detect mechanical inputs and shape mechanoreceptor adaptation.     

Touch sense

Cutaneous mechanoreceptors are localized in the various layers of the skin where they detect a wide range of mechanical stimuli, including light brush, stretch, vibration and noxious pressure. This variety of stimuli is matched by a diverse array of specialized mechanoreceptors that respond to cutaneous deformation in a specific way and relay these stimuli to higher brain structures. Studies across mechanoreceptors and genetically tractable sensory nerve endings are beginning to uncover touch sensation mechanisms. Work in this field has provided researchers with a more thorough understanding of the circuit organization underlying the perception of touch. Novel ion channels have emerged as candidates for transduction molecules and properties of mechanically gated currents improved our understanding of the mechanisms of adaptation to tactile stimuli. This review highlights the progress made in characterizing functional properties of mechanoreceptors in hairy and glabrous skin and ion channels that detect mechanical inputs and shape mechanoreceptor adaptation.     

External sensilla of the locust abdomen provide the central nervous system with an interganglionic network

External mechanoreceptors and contact chemoreceptors on the cuticle of the sixth abdominal segment of locusts have divergent primary projections of their sensory neurons that form arbours in the segmental and anterior abdominal ganglia. Homologous interganglionic projections from adjacent segments converge in the neuropile of each abdominal ganglion. Of the contributing types of sensilla, three were previously unknown for locust pregenital segments: tactile mechanosensory hairs with dual innervation, external proprioceptors of the hairplate type covered by intersegmental membranes and single campaniform sensilla that monitor cuticular strain in sternites and tergites. In general, interdependence of motor coordination in the abdominal segments is based on a neural network that relies heavily on intersegmental primary afferents that cooperate to identify the location, parameters and strength of external stimuli.     

Responses of cutaneous mechanoreceptors within fingerpad to stimulus information for tactile softness sensation of materials

Softness sensation is one of primitive tactile textures. While the psychophysical characteristics of softness sensation have been thoroughly studied, it is lack of a deep understanding of the underlying neuromechanical principles. On the stimulus–response processes of human fingerpad touching fabrics and the physiological properties of slowly adapting type I (SAIs) cutaneous mechanoreceptors within fingerpad, a fabric-skin-receptor coupling model was built and validated. By the fabric-skin-receptor model a series of numerical experiments was conducted, and how the evoked neural responses of cutaneous mechanoreceptors change with the composite compliance of both fingerpad skin and the materials in contact was investigated. The results indicated that the evoked neural responses of populations of cutaneous mechanoreceptors by the physical stimulus from fabrics were nearly proportional to the perceived softness magnitude, and nonlinearly increased and then decreased with the effective elastic modulus of fabrics or the relative elastic modulus of fabrics to soft tissues within fingerpad, where the nonlinear inflection point depended on the touching force level. Therefore, it concluded that the tactile judgment of the physical information for softness sensation of objects was an encoding of neural responses of populations of SAIs cutaneous mechanoreceptors, and the physical information depended on the mechanical interaction of fingerpad and objects in contact.     

How does the toad's visual system discriminate different worm-like stimuli?

Behavioral experiments show that toads exhibit stimulus- and locus-specific habituation. Different worm-like stimuli that toads can discriminate at a certain visual location form a dishabituation hierarchy. What is the neural mechanism which underlies these behaviors? This paper proposes that the toad discriminates visual objects based on temporal responses, and that discrimination is reflected in different average neuronal firing rates at some higher visual center, hypothetically anterior thalamus. This theory is developed through a large-scale neural simulation which includes retina, tectum and anterior thalamus. The neural model based on this theory predicts that retinal R2 cells play a primary role in the discrimination via tectal small pear cells (SP) and R3 cells refine the feature analysis by inhibition. The simulation demonstrates that the retinal response to the trailing edge of a stimulus is as crucial for pattern discrimination as the response to the leading edge. The new dishabituation hierarchies predicted by this model by reversing contrast and shrinking stimulus size need to be tested experimentally.     

Vibrotactile thresholds at the fingertip, volar forearm, large toe, and heel

Thresholds for the perception of vibration vary with location on the body due to the organization of tactile channels in hairy and non-hairy skin, and variations in receptor density. This study determined vibration thresholds at four locations on the body with two different contactors so as to assist the identification of the tactile channel determining the threshold at each location. Vibrotactile thresholds at six frequencies from 8 to 250 Hz were measured on the distal phalanx of the index finger, the volar forearm, the large toe, and the heel with two contactors: (i) a 1-mm diameter circular probe with a 1-mm gap to a fixed circular surround (i.e., 7.1-mm(2) excitation area), and (ii) a 6-mm diameter circular probe with a 2-mm gap to a fixed circular surround (i.e., 79-mm(2) excitation area). At all frequencies and with both contactors, thresholds on the fingertip were lower than thresholds on the volar forearm, the large toe, and the heel, consistent with a greater density of mechanoreceptors at the fingertip. Thresholds with the larger contactor were lower than thresholds with the smaller contactor on the fingertip at high frequencies (63, 125, and 250 Hz), on the large toe (except at 250 Hz), on the heel (at all frequencies), and on the volar forearm at 250 Hz. It is concluded that at least two tactile channels (Pacinian from 63 to 250 Hz, and non-Pacinian from 8 to 31.5 Hz) determined vibrotactile thresholds at the fingertip, whereas non-Pacinian channels had a dominant influence on vibrotactile thresholds at the volar forearm. The role of Pacinian and non-Pacinian channels could not be confirmed at the large toe or the heel despite some evidence of spatial summation.     

Velocity and displacement receptors in the skin of the hagfish Myxine glutinosa.

The skin of Myxine glutinosn contains both velocity-sensitive and displacement-sensitive mechanoreceptors. These can be distinguished from each other by the different time course of their response to skin indentation. Velocity receptors gave a brief response, consisting usually of three to four action potentials which could only be elicited by movement of the skin. No velocity receptor was spontaneously active. Displacement receptors, some of which were spontaneously active, gave a prolonged discharge which continued, with only slight adaptation, while the skin was indented. Velocity receptors code for velocity of indentation and continue to respond to repeated stimuli. Displacement receptor action potentials occur irregularly, with a Poisson-like distribution of interspike interval. The mean frequency of displacement receptor discharge increases with depth of skin indentation, while the interspike interval distribution becomes progressively biased towards shorter intervals. The threshold of displacement receptors is related to displacement velocity; sinusoidal indentations of the skin produce a minimum threshold around 60 Hz. These receptors fail to respond to oscillations in excess of 120 Hz. The structure of the skin is described. Stress-strain curves are given both for static and dynamic compression of the skin and these are discussed in relation to the properties of the skin mechanoreceptors.     

Tactile receptor discharge and mechanical properties of glabrous skin

Current knowledge of the functional properties of mammalian cutaneous mechanoreceptors is reviewed with special reference to receptors associated with the glabrous skin of the raccoon and squirrel monkey hand. Four physiologically defined mechanoreceptor types are recognized: Pacinian afferents, rapidly adapting (RA), and slowly adapting type I (SAI), and slowly adapting type II (SAII). The SAI category is divided into moderately slowly adapting and very slowly adapting (VSA) types in terms of the duration of their response to a prolonged mechanical displacement of skin. Although both RA and SA units are capable of signaling displacement ramp velocity, the pattern of discharge during ramp stimulation may vary widely among units. SAI units also code the depth of skin displacement, but there is no best-fitting function describing the relationship. Static discharge is also markedly influenced by prior ramp velocity. Both raccoon and squirrel monkey VSA units show wide variation in the regularity of their discharge during static displacement. The rate of adaptation of SAI units is less when constant force stimuli are applied to the skin than when constant displacement stimuli are applied. This is partly attributable to mechanical properties of the skin. When either constant force or constant displacement stimuli are spaced too closely in time, there is a progressive (trial-to-trial) decrement in response rate, accounted for in part by failure of the skin to recover to its initial resting level.     

Adaptive cardiovascular modifications in the western chipmunks genusEutamias

Summary Although cutaneous type I and type II mechanoreceptors in the cat respond at progressively higher frequencies to increasingly rapid skin indentations of suprathreshold intensity, their thresholds are not lowered when these more rapid stimuli are applied. Since these receptors do not selectively detect rapid stimuli of small amplitude, even though they respond much more vigorously to a suprathreshold stimulus that is rapid, different parameters of the stimulus are signalled depending on whether it is near threshold or clearly suprathreshold.This work was supported by grant GB42643 from the National Science Foundation and by grants NS08769, NS07938 and NS05244 from the U.S. Public Health ServiceThe authors thank John Fisher, Gary Frederickson, Tom O'Leary, Robert Perry, and Jane Burgess for their valuable help.     

Analysis of the dynamic strains in a fingertip exposed to vibrations: Correlation to the mechanical stimuli on mechanoreceptors

The reduction in vibrotactile sensitivity in the fingertip is assumed to be associated with the exposure of the tissues to repetitive, non-physiological strains during dynamic loading. Experimental results demonstrated that the magnitude of a vibration-induced temporary threshold shift is dependent upon the vibration frequency of both the exposure and testing stimuli. In the present study, the frequency-dependent strain imposed on cutaneous and subcutaneous tissues of the fingertip is analyzed theoretically using a finite element model. The proposed fingertip model is two-dimensional and includes major anatomical substructures: skin, subcutaneous tissue, bone, and nail. The soft tissues (skin and subcutaneous tissues) were assumed to be nonlinearly elastic and viscoelastic, while the bone and nail were considered as linearly elastic. Simulations were performed for the contact between the fingertip and a flat surface for four different pre-compressions (0.5, 1.0, 1.5, and 2.0 mm). The frequency-dependent distributions of the dynamic strain magnitudes in the soft tissues were investigated. The model predictions indicated that the vibration exposure at a frequency range from 63 to 250 Hz will induce excessive dynamic strain in the deep zone of the finger tissues, effectively inhibiting the high-frequency mechanoreceptors; while the vibration exposure at low frequency (less than 31.5 Hz) tends to induce excessive dynamic strain in superficial layer in the tissues, inhibiting the low-frequency mechanoreceptors. These theoretical predictions are consistent with the experimental observations in literature. The proposed model can be used to predict the responses of the soft tissues in different depths to vibration exposures, providing valuable information and data that are essential for improving vibrotactile perception tests.     

An attempt to determine the structure of the nervous system serving mechanoreceptors

Following disparities between physical stimuli and psychophysically measured sensation patterns are investigated: 1. long or short duration stimulation of the same area on the skin produces different sensation patterns. No transient response is observed. 2. when a set of points on the skin is stimulated one by one at the rate, at least 2 points per second, the subject perceives easily readible, continuously moving tactual sensation. As the rate of stimulation of the same points increases, the trajectory of the sensation changes. Investigations regarding the above distortions, supplemented with other experiments, lead to some conclusions concerning the structure of the nervous system serving mechanoreceptors, and show the connections between psychophysical, electrophysiological and theoretical observations of this system.     

Hyperelastic Material Properties of Mouse Skin under Compression

The skin is a dynamic organ whose complex material properties are capable of withstanding continuous mechanical stress while accommodating insults and organism growth. Moreover, synchronized hair cycles, comprising waves of hair growth, regression and rest, are accompanied by dramatic fluctuations in skin thickness in mice. Whether such structural changes alter skin mechanics is unknown. Mouse models are extensively used to study skin biology and pathophysiology, including aging, UV-induced skin damage and somatosensory signaling. As the skin serves a pivotal role in the transfer function from sensory stimuli to neuronal signaling, we sought to define the mechanical properties of mouse skin over a range of normal physiological states. Skin thickness, stiffness and modulus were quantitatively surveyed in adult, female mice (Mus musculus). These measures were analyzed under uniaxial compression, which is relevant for touch reception and compression injuries, rather than tension, which is typically used to analyze skin mechanics. Compression tests were performed with 105 full-thickness, freshly isolated specimens from the hairy skin of the hind limb. Physiological variables included body weight, hair-cycle stage, maturity level, skin site and individual animal differences. Skin thickness and stiffness were dominated by hair-cycle stage at young (6–10 weeks) and intermediate (13–19 weeks) adult ages but by body weight in mature mice (26–34 weeks). Interestingly, stiffness varied inversely with thickness so that hyperelastic modulus was consistent across hair-cycle stages and body weights. By contrast, the mechanics of hairy skin differs markedly with anatomical location. In particular, skin containing fascial structures such as nerves and blood vessels showed significantly greater modulus than adjacent sites. Collectively, this systematic survey indicates that, although its structure changes dramatically throughout adult life, mouse skin at a given location maintains a constant elastic modulus to compression throughout normal physiological stages.     

The DRASIC cation channel contributes to the detection of cutaneous touch and acid stimuli in mice.

Cation channels in the DEG/ENaC family are proposed to detect cutaneous stimuli in mammals. We localized one such channel, DRASIC, in several different specialized sensory nerve endings of skin, suggesting it might participate in mechanosensation and/or acid-evoked nociception. Disrupting the mouse DRASIC gene altered sensory transduction in specific and distinct ways. Loss of DRASIC increased the sensitivity of mechanoreceptors detecting light touch, but it reduced the sensitivity of a mechanoreceptor responding to noxious pinch and decreased the response of acid- and noxious heat-sensitive nociceptors. The data suggest that DRASIC subunits participate in heteromultimeric channel complexes in sensory neurons. Moreover, in different cellular contexts, DRASIC may respond to mechanical stimuli or to low pH to mediate normal touch and pain sensation.     

Integrating individual search and navigation behaviors in mechanistic movement models

Understanding complex movement behaviors via mechanistic models is one key challenge in movement ecology. We built a theoretical simulation model using evolutionarily trained artificial neural networks (ANNs) wherein individuals evolve movement behaviors in response to resource landscapes on which they search and navigate. We distinguished among non-oriented movements in response to proximate stimuli, oriented movements utilizing perceptual cues from distant targets, and memory mechanisms that assume prior knowledge of a target??s location and then tested the relevance of these three movement behaviors in relation to size of resource patches, predictability of resource landscapes, and the occurrence of movement barriers. Individuals were more efficient in locating resources under larger patch sizes and predictable landscapes when memory was advantageous. However, memory was also frequently used in unpredictable landscapes with intermediate patch sizes to systematically search the entire spatial domain, and because of this, we suggest that memory may be important in explaining super-diffusion observed in many empirical studies. The sudden imposition of movement barriers had the greatest effect under predictable landscapes and temporarily eliminated the benefits of memory. Overall, we demonstrate how movement behaviors that are linked to certain cognitive abilities can be represented by state variables in ANNs and how, by altering these state variables, the relevance of different behaviors under different spatiotemporal resource dynamics can be tested. If adapted to fit empirical movement paths, methods described here could help reveal behavioral mechanisms of real animals and predict effects of anthropogenic landscape changes on animal movement.     

Loss of SED1/MFG‐E8 results in altered luminal physiology in the epididymis

SED1/MFG‐E8, herein referred to as SED1, is a bimotif adhesive protein with ascribed functions in a range of cell–cell interactions, including sperm‐egg binding. In the male reproductive tract, SED1 is secreted by the initial segment of the epididymis, where it coats sperm and subsequently facilitates binding to the egg zona pellucida. We have recently reported that SED1‐null epididymides show an unexpected incidence of spermatic granulomas, reflecting breakdown of the epithelium and a consequent autoimmune response against sperm antigens. However, spermatic granulomas are most often manifest in the distal segments of the epididymis, whereas the bulk of SED1 is expressed in the proximal epididymis. In some models, the presence of granulomas in the distal epididymis is associated with an underlying defect in the maintenance of luminal fluid homeostasis. Herein, we report that SED1‐null epididymal fluid is both hypo‐osmotic and alkaline, relative to wildtype epididymal fluid. Furthermore, the SED1‐null epididymal epithelium exhibits various hallmarks of disrupted fluid reabsorption and pH regulation, including altered morphology of clear cells, increased intracellular vesicles, and apical distribution of VATPase. Results indicate that the SED1‐null epididymal pathologies are not the secondary consequences of defective testes or efferent ducts or of improper epididymal differentiation, unlike that seen in other epididymal models. The expression and distribution of various ion exchangers, channels, and enzymes that mediate fluid transport and pH regulation are examined in wildtype and SED1‐null epididymides, and models to account for how SED1 functions in luminal fluid dynamics are discussed. Mol. Reprod. Dev. 77: 550–563, 2010. © 2010 Wiley‐Liss, Inc.