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The Journal of Neuroscience : the... Oct 2016Axon-Schwann cell interactions are crucial for the development, function, and repair of the peripheral nervous system, but mechanisms underlying communication between...
UNLABELLED
Axon-Schwann cell interactions are crucial for the development, function, and repair of the peripheral nervous system, but mechanisms underlying communication between axons and nonmyelinating Schwann cells are unclear. Here, we show that ER81 is functionally required in a subset of mouse RET mechanosensory neurons for formation of Pacinian corpuscles, which are composed of a single myelinated axon and multiple layers of nonmyelinating Schwann cells, and Ret is required for the maintenance of Er81 expression. Interestingly, Er81 mutants have normal myelination but exhibit deficient interactions between axons and corpuscle-forming nonmyelinating Schwann cells. Finally, ablating Neuregulin-1 (Nrg1) in mechanosensory neurons results in no Pacinian corpuscles, and an Nrg1 isoform not required for communication with myelinating Schwann cells is specifically decreased in Er81-null somatosensory neurons. Collectively, our results suggest that a RET-ER81-NRG1 signaling pathway promotes axon communication with nonmyelinating Schwann cells, and that neurons use distinct mechanisms to interact with different types of Schwann cells.
SIGNIFICANCE STATEMENT
Communication between neurons and Schwann cells is critical for development, normal function, and regeneration of the peripheral nervous system. Despite many studies about axonal communication with myelinating Schwann cells, mostly via a specific isoform of Neuregulin1, the molecular nature of axonal communication with nonmyelinating Schwann cells is poorly understood. Here, we described a RET-ER81-Neuregulin1 signaling pathway in neurons innervating Pacinian corpuscle somatosensory end organs, which is essential for communication between the innervating axon and the end organ nonmyelinating Schwann cells. We also showed that this signaling pathway uses isoforms of Neuregulin1 that are not involved in myelination, providing evidence that neurons use different isoforms of Neuregulin1 to interact with different types of Schwann cells.
Topics: Animals; Axons; DNA-Binding Proteins; Mechanotransduction, Cellular; Mice; Mice, Inbred C57BL; Mutation; Myelin Sheath; Neuregulin-1; Neurons; Pacinian Corpuscles; Peripheral Nerve Injuries; Proto-Oncogene Proteins c-ret; Schwann Cells; Signal Transduction; Transcription Factors
PubMed: 27707970
DOI: 10.1523/JNEUROSCI.2160-16.2016 -
Journal of Applied Physiology... Apr 2016It has previously been shown that cutaneous sensory input from across a broad region of skin can influence proprioception at joints of the hand. The present experiment...
It has previously been shown that cutaneous sensory input from across a broad region of skin can influence proprioception at joints of the hand. The present experiment tested whether cutaneous input from different skin regions across the foot can influence proprioception at the ankle joint. The ability to passively match ankle joint position (17° and 7° plantar flexion and 7° dorsiflexion) was measured while cutaneous vibration was applied to the sole (heel, distal metatarsals) or dorsum of the target foot. Vibration was applied at two different frequencies to preferentially activate Meissner's corpuscles (45 Hz, 80 μm) or Pacinian corpuscles (255 Hz, 10 μm) at amplitudes ∼3 dB above mean perceptual thresholds. Results indicated that cutaneous input from all skin regions across the foot could influence joint-matching error and variability, although the strongest effects were observed with heel vibration. Furthermore, the influence of cutaneous input from each region was modulated by joint angle; in general, vibration had a limited effect on matching in dorsiflexion compared with matching in plantar flexion. Unlike previous results in the upper limb, we found no evidence that Pacinian input exerted a stronger influence on proprioception compared with Meissner input. Findings from this study suggest that fast-adapting cutaneous input from the foot modulates proprioception at the ankle joint in a passive joint-matching task. These results indicate that there is interplay between tactile and proprioceptive signals originating from the foot and ankle.
Topics: Adult; Ankle; Ankle Joint; Female; Foot; Hand; Heel; Humans; Male; Mechanoreceptors; Muscle, Skeletal; Neurons, Afferent; Pacinian Corpuscles; Proprioception; Skin; Touch; Vibration; Young Adult
PubMed: 26823342
DOI: 10.1152/japplphysiol.00810.2015 -
Proceedings of the National Academy of... Dec 2015Interactions with the physical world are deeply rooted in our sense of touch and depend on ensembles of somatosensory neurons that invade and innervate the skin....
Interactions with the physical world are deeply rooted in our sense of touch and depend on ensembles of somatosensory neurons that invade and innervate the skin. Somatosensory neurons convert the mechanical energy delivered in each touch into excitatory membrane currents carried by mechanoelectrical transduction (MeT) channels. Pacinian corpuscles in mammals and touch receptor neurons (TRNs) in Caenorhabditis elegans nematodes are embedded in distinctive specialized accessory structures, have low thresholds for activation, and adapt rapidly to the application and removal of mechanical loads. Recently, many of the protein partners that form native MeT channels in these and other somatosensory neurons have been identified. However, the biophysical mechanism of symmetric responses to the onset and offset of mechanical stimulation has eluded understanding for decades. Moreover, it is not known whether applied force or the resulting indentation activate MeT channels. Here, we introduce a system for simultaneously recording membrane current, applied force, and the resulting indentation in living C. elegans (Feedback-controlled Application of mechanical Loads Combined with in vivo Neurophysiology, FALCON) and use it, together with modeling, to study these questions. We show that current amplitude increases with indentation, not force, and that fast stimuli evoke larger currents than slower stimuli producing the same or smaller indentation. A model linking body indentation to MeT channel activation through an embedded viscoelastic element reproduces the experimental findings, predicts that the TRNs function as a band-pass mechanical filter, and provides a general mechanism for symmetrical and rapidly adapting MeT channel activation relevant to somatosensory neurons across phyla and submodalities.
Topics: Animals; Caenorhabditis elegans; Mammals; Mechanotransduction, Cellular; Physical Stimulation; Touch
PubMed: 26627717
DOI: 10.1073/pnas.1514138112 -
Journal of Clinical and Diagnostic... Sep 2015Pacinian neuromas are rare benign tumours of pacinian corpuscles of the digits. They generally occur on the volar aspect of the fingertips. Pacinian corpuscles are...
Pacinian neuromas are rare benign tumours of pacinian corpuscles of the digits. They generally occur on the volar aspect of the fingertips. Pacinian corpuscles are specialised nerve endings with a lamellated structure and are regarded as pressure and vibration receptors. Here, we report a case of pacinian neuroma presenting as congenital macrodactyly of the right little finger with pain for which the lesion was surgically excised.
PubMed: 26500954
DOI: 10.7860/JCDR/2015/14525.6528 -
Arthroscopy : the Journal of... Feb 2016To investigate the morphology and quantity of mechanoreceptors in the remnant stumps of injured anterior cruciate ligaments (ACLs) and the association of the number of...
PURPOSE
To investigate the morphology and quantity of mechanoreceptors in the remnant stumps of injured anterior cruciate ligaments (ACLs) and the association of the number of mechanoreceptors with the time from injury to surgery.
METHODS
Complete ACL stump specimens were collected from 40 volunteer patients who underwent arthroscopic ACL reconstruction surgery. Serial sections, 20 μm in thickness, were prepared from each specimen. After H&E staining and immunohistochemical labeling, the morphology, type, size, and quantity of the mechanoreceptors were observed under an optical microscope.
RESULTS
A total of 176 Ruffini corpuscles, 61 pacinian corpuscles, 15 Golgi-like tendon organs, and 66 atypical mechanoreceptors were observed. Free nerve endings were commonly present in the specimens. The time from injury to surgery (log10 days) was negatively correlated with the number of total mechanoreceptors (r = -0.43, P < .006), Ruffini corpuscles (r = -0.45, P < .003), and the volume of the ACL stump (r = -0.52, P < .01), and these correlations were independent of age, gender, injury side, and career.
CONCLUSIONS
The number of mechanoreceptors in an ACL stump and the volume of the stump decreased with the time from injury to surgery.
CLINICAL RELEVANCE
This study provides a further theoretical basis for ACL reconstruction with remnant preservation.
Topics: Adult; Anterior Cruciate Ligament; Anterior Cruciate Ligament Injuries; Anterior Cruciate Ligament Reconstruction; Arthroscopy; Female; Humans; Immunohistochemistry; Male; Mechanoreceptors; Staining and Labeling; Young Adult
PubMed: 26422704
DOI: 10.1016/j.arthro.2015.07.010 -
PLoS Computational Biology Sep 2015Cutaneous mechanoreceptors transduce different tactile stimuli into neural signals that produce distinct sensations of touch. The Pacinian corpuscle (PC), a cutaneous...
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.
Topics: Anisotropy; Computational Biology; Humans; Models, Biological; Pacinian Corpuscles
PubMed: 26390130
DOI: 10.1371/journal.pcbi.1004370 -
Journal of Orthopaedic Surgery and... Jun 2015The aim of this study was to analyze the pattern and types of sensory nerve endings in ankle collateral ligaments using histological techniques, in order to observe the...
BACKGROUND
The aim of this study was to analyze the pattern and types of sensory nerve endings in ankle collateral ligaments using histological techniques, in order to observe the morphology and distribution of mechanoreceptors in the collateral ligaments of cadaver ankle joint, and to provide the morphological evidence for the role of the ligament in joint sensory function.
METHODS
Twelve lateral collateral ligaments including anterior talofibular ligament (ATFL; n = 6), posterior talofibular ligament (PTFL; n = 6), and calcaneofibular ligament (CFL; n = 6) were harvested from six fresh frozen cadavers. The ligaments were embedded in paraffin, sectioned at 4 μm, and then stained using a modified gold-chloride staining methods. The collateral ligament was divided into three segments: proximal, middle, and distal segments. Fifty-four ATFL slides, 90 PTFL slides, and 108 CFL slides were analyzed. Mechanoreceptors were classified based on Freemen and Wyke's classification. Mechanoreceptor distribution was analyzed statistically. One-way ANOVA (postHoc LSD) was used for statistical analysis.
RESULTS
All the four typical types of nerve endings (the Ruffini corpuscles, Pacinian corpuscles, Golgi tendon organs, and free nerve endings) were identified in these ligaments. Pacinian corpuscles were the predominant in all four complexes. More mechanoreceptors were found in synovial membrane near both ends of the ligaments attached to the bone. No statistical differences were found in the amount of mechanoreceptors among distal, middle, and proximal parts of the ligaments.
CONCLUSIONS
The four typical types of mechanoreceptors were all identified in the collateral ligaments of the human ankle. Pacinian corpuscles were the predominant in all four complexes. This indicates that the main function of ankle collateral ligaments is to sense joint speeds in motions.
Topics: Adult; Female; Gold Compounds; Humans; Lateral Ligament, Ankle; Male; Mechanoreceptors; Middle Aged; Young Adult
PubMed: 26063220
DOI: 10.1186/s13018-015-0215-7 -
Science (New York, N.Y.) Nov 2014The skin is our largest sensory organ, transmitting pain, temperature, itch, and touch information to the central nervous system. Touch sensations are conveyed by... (Review)
Review
The skin is our largest sensory organ, transmitting pain, temperature, itch, and touch information to the central nervous system. Touch sensations are conveyed by distinct combinations of mechanosensory end organs and the low-threshold mechanoreceptors (LTMRs) that innervate them. Here we explore the various structures underlying the diverse functions of cutaneous LTMR end organs. Beyond anchoring of LTMRs to the surrounding dermis and epidermis, recent evidence suggests that the non-neuronal components of end organs play an active role in signaling to LTMRs and may physically gate force-sensitive channels in these receptors. Combined with LTMR intrinsic properties, the balance of these factors comprises the response properties of mechanosensory neurons and, thus, the neural encoding of touch.
Topics: Animals; Dermis; Epidermis; Hair; Hair Follicle; Humans; Mechanoreceptors; Mechanotransduction, Cellular; Merkel Cells; Neurons; Pacinian Corpuscles; Touch
PubMed: 25414303
DOI: 10.1126/science.1254229 -
Journal of Neurophysiology Feb 2015The goal of this review is to start to consolidate and distill the substantial body of research that comprises the published work of the late Professor Steven S. Hsiao.... (Review)
Review
The goal of this review is to start to consolidate and distill the substantial body of research that comprises the published work of the late Professor Steven S. Hsiao. The studies of Hsiao began by demonstrating the receptive field properties of somatosensory neurons, progressed to describing cortical feature selectivity, and then eventually elevated the field to hopes of tapping into natural neural codes with artificial somatosensory feedback. With ongoing analogies to contemporaneous studies in visual neuroscience, the research results and writings of Hsiao have provided the fields of haptics and somatosensory neurophysiology with the conceptual tools needed to allow profound progress. Specifically, Hsiao suggested that slowly adapting tactile form perception could be restored with cortical microstimulation, rapidly adapting slip reflexes should be relegated to low-level, hard-wired prosthetic components, and Pacinian-corpuscle spatiotemporal population responses could potentially be decoded/encoded to provide information about interactions of hands and hand-held instruments with external objects. Future studies will be guided by these insightful reports from Hsiao.
Topics: Animals; Evoked Potentials, Somatosensory; Humans; Somatosensory Cortex; Touch Perception
PubMed: 25392173
DOI: 10.1152/jn.00670.2014 -
Anatomical Record (Hoboken, N.J. : 2007) Mar 2015Some mechanoreceptors in mammals depend totally or in part on the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4), and their receptor...
Some mechanoreceptors in mammals depend totally or in part on the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4), and their receptor TrkB, for development and maintenance. These actions are presumably exerced regulating the survival of discrete sensory neurons in the dorsal root ganglia which form mechanoreceptors at the periphery. In addition, the cells forming the mechanoreceptors also express both neurotrophins and their receptors although large differences have been described among species. Pacinian corpuscles are rapidly adapting low-threshold mechanoreceptors whose dependence from neurotrophins is not known. In the present study, we analyzed expression of TrkB and their ligands BDNF and NT-4 in the cutaneous Pacinian corpuscles of Macaca fascicularis using immunohistochemistry and fluorescent microscopy. TrkB immunoreactivity was found in Pacinian corpuscles where it co-localized with neuron-specific enolase, and occasionally with S100 protein, thus suggesting that TrkB expression is primarily into axons but also in the lamellar cells and even in the outer core. On the other hand, BDNF immunoreactivity was found the inner core cells where it co-localized with S100 protein but also in the innermost layers of the outer core; NT-4 immunostaining was not detected. These results describe for the first time the expression and distribution of a full neurotrophin system in the axon-inner core complex of mature Pacinian corpuscles. The data support previous findings demonstrating large differences in the expression of BDNF-TrkB in mammalian mechanoreceptors, and also suggest the existence of a retrograde trophic signaling mechanism to maintain morphological and functional integrity of sensory neurons supplying Pacinian corpuscles.
Topics: Animals; Brain-Derived Neurotrophic Factor; Macaca fascicularis; Male; Pacinian Corpuscles; Receptor, trkB
PubMed: 25230956
DOI: 10.1002/ar.23050