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Gary R Lewin - One of the best experts on this subject based on the ideXlab platform.
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the transcription factor c maf controls touch receptor development and function
Science, 2012Co-Authors: Hagen Wende, Patrick Carroll, Stefan G. Lechner, Cyril Cheret, Steeve Bourane, Maria E Kolanczyk, Alexandre Pattyn, Katja Reuter, Francis L Munier, Gary R LewinAbstract:The sense of touch relies on detection of mechanical stimuli by specialized mechanosensory neurons. The scarcity of molecular data has made it difficult to analyze development of Mechanoreceptors and to define the basis of their diversity and function. We show that the transcription factor c-Maf/c-MAF is crucial for mechanosensory function in mice and humans. The development and function of several rapidly adapting mechanoreceptor types are disrupted in c-Maf mutant mice. In particular, Pacinian corpuscles, a type of mechanoreceptor specialized to detect high-frequency vibrations, are severely atrophied. In line with this, sensitivity to high-frequency vibration is reduced in humans carrying a dominant mutation in the c-MAF gene. Thus, our work identifies a key transcription factor specifying development and function of Mechanoreceptors and their end organs.
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kcnq4 k channels tune Mechanoreceptors for normal touch sensation in mouse and man
Nature Neuroscience, 2012Co-Authors: Matthias Heidenreich, Thomas J. Jentsch, Christiane Wetzel, Stefan G. Lechner, Vitya Vardanyan, Cor W. R. J. Cremers, Els De Leenheer, Gracia Aránguez, M A Morenopelayo, Gary R LewinAbstract:Mutations inactivating the potassium channel KCNQ4 (K(v)7.4) lead to deafness in humans and mice. In addition to its expression in mechanosensitive hair cells of the inner ear, KCNQ4 is found in the auditory pathway and in trigeminal nuclei that convey somatosensory information. We have now detected KCNQ4 in the peripheral nerve endings of cutaneous rapidly adapting hair follicle and Meissner corpuscle Mechanoreceptors from mice and humans. Electrophysiological recordings from single afferents from Kcnq4(-/-) mice and mice carrying a KCNQ4 mutation found in DFNA2-type monogenic dominant human hearing loss showed elevated mechanosensitivity and altered frequency response of rapidly adapting, but not of slowly adapting nor of D-hair, mechanoreceptor neurons. Human subjects from independent DFNA2 pedigrees outperformed age-matched control subjects when tested for vibrotactile acuity at low frequencies. This work describes a gene mutation that modulates touch sensitivity in mice and humans and establishes KCNQ4 as a specific molecular marker for rapidly adapting Meissner and a subset of hair follicle afferents.
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KCNQ4 K(+) channels tune Mechanoreceptors for normal touch sensation in mouse and man.
Nature neuroscience, 2011Co-Authors: Matthias Heidenreich, Christiane Wetzel, Stefan G. Lechner, Vitya Vardanyan, Cor W. R. J. Cremers, Els De Leenheer, Gracia Aránguez, M A Moreno-pelayo, Gary R LewinAbstract:Mutations inactivating the potassium channel KCNQ4 (K(v)7.4) lead to deafness in humans and mice. In addition to its expression in mechanosensitive hair cells of the inner ear, KCNQ4 is found in the auditory pathway and in trigeminal nuclei that convey somatosensory information. We have now detected KCNQ4 in the peripheral nerve endings of cutaneous rapidly adapting hair follicle and Meissner corpuscle Mechanoreceptors from mice and humans. Electrophysiological recordings from single afferents from Kcnq4(-/-) mice and mice carrying a KCNQ4 mutation found in DFNA2-type monogenic dominant human hearing loss showed elevated mechanosensitivity and altered frequency response of rapidly adapting, but not of slowly adapting nor of D-hair, mechanoreceptor neurons. Human subjects from independent DFNA2 pedigrees outperformed age-matched control subjects when tested for vibrotactile acuity at low frequencies. This work describes a gene mutation that modulates touch sensitivity in mice and humans and establishes KCNQ4 as a specific molecular marker for rapidly adapting Meissner and a subset of hair follicle afferents.
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role of t type calcium current in identified d hair mechanoreceptor neurons studied in vitro
The Journal of Neuroscience, 2004Co-Authors: Annesophie Dubreuil, Carlos Martinezsalgado, Gary R Lewin, Hassan Boukhaddaoui, Gilles Desmadryl, Rabih Moshourab, Patrick Carroll, Jean Valmier, Frederique ScampsAbstract:Different subsets of dorsal root ganglion (DRG) Mechanoreceptors transduce low- and high-intensity mechanical stimuli. It was shown recently that, in vivo, neurotrophin-4 (NT-4)-dependent D-hair Mechanoreceptors specifically express a voltage-activated T-type calcium channel (Cav3.2) that may be required for their mechanoreceptive function. Here we show that D-hair Mechanoreceptors can be identified in vitro by a rosette-like morphology in the presence of NT-4 and that these rosette neurons are almost all absent in DRG cultures taken from NT-4 knock-out mice. In vitro identification of the D-hair mechanoreceptor allowed us to explore the electrophysiological properties of these cells. We demonstrate that the T-type Cav3.2 channel induced slow membrane depolarization that contributes to lower the voltage threshold for action potential generation and controls spike latency after stimulation of D-hair Mechanoreceptors. Indeed, the properties of the T-type amplifier are particularly well suited to explain the high sensitivity of D-hair Mechanoreceptors to slowly moving stimuli.
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a t type calcium channel required for normal function of a mammalian mechanoreceptor
Nature Neuroscience, 2003Co-Authors: Jungbum Shin, Carlos Martinezsalgado, Paul A Heppenstall, Gary R LewinAbstract:The dorsal root ganglia (DRG) contain a variety of Mechanoreceptors, but no molecular markers uniquely identify specific mechanoreceptor subtypes. We have used DNA microarrays and subtracted cDNA libraries to isolate genes that are specifically expressed by one type of mouse mechanoreceptor. The T-type calcium channel Cav3.2 was exclusively expressed in the DRG by D-hair receptors, a very sensitive mechanoreceptor. Pharmacological blockade of T-type calcium channels indicated that this channel may be essential for normal D-hair receptor excitability including mechanosensitivity. This is the first evidence that a calcium channel is required for normal function of a vertebrate mechanoreceptor.
Robyn A Grant - One of the best experts on this subject based on the ideXlab platform.
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anatomy of avian rictal bristles in caprimulgiformes reveals reduced tactile function in open habitat partially diurnal foraging species
Journal of Anatomy, 2020Co-Authors: Mariane G Delaunay, Carl Larsen, Huw Lloyd, Matthew Sullivan, Robyn A GrantAbstract:: Avian rictal bristles are present in many species of birds, especially in nocturnal species. Rictal bristles occur along the upper beak and are morphologically similar to mammalian whiskers. Mammalian whiskers are important tactile sensors, guiding locomotion, foraging and social interactions, and have a well-characterised anatomy. However, it is not yet known whether avian rictal bristles have a sensory function, and their morphology, anatomy and function have also not been described in many species. Our study compares bristle morphology, follicle anatomy and their association with foraging traits, across 12 Caprimulgiform species. Rictal bristle morphology and follicle anatomy were diverse across the 12 species. Nine of the 12 species had Mechanoreceptors around their bristle follicles; however, there was large variation in their musculature, mechanoreceptor numbers and bristle morphology. Overall, species with short, thin, branching bristles that lacked Mechanoreceptors tended to forage pre-dusk in open habitats, whereas species with Mechanoreceptors around their bristle follicle tended to forage at night and in more closed habitats. We suggest that rictal bristles are likely to be tactile in many species and may aid in navigation, foraging and collision avoidance; however, identifying rictal bristle function is challenging and demands further investigation in many species.
Christiane Wetzel - One of the best experts on this subject based on the ideXlab platform.
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Small-molecule inhibition of STOML3 oligomerization reverses pathological mechanical hypersensitivity
Nature Neuroscience, 2017Co-Authors: Christiane Wetzel, Simone Pifferi, Cristina Picci, Caglar Gök, Diana Hoffmann, Kiran Bali, André Lampe, Liudmila Lapatsina, Raluca Fleischer, Ewan St John SmithAbstract:The skin is equipped with specialized Mechanoreceptors that allow the perception of the slightest brush. Indeed, some Mechanoreceptors can detect even nanometer-scale movements. Movement is transformed into electrical signals via the gating of mechanically activated ion channels at sensory endings in the skin. The sensitivity of Piezo mechanically gated ion channels is controlled by stomatin-like protein-3 (STOML3), which is required for normal mechanoreceptor function. Here we identify small-molecule inhibitors of STOML3 oligomerization that reversibly reduce the sensitivity of mechanically gated currents in sensory neurons and silence Mechanoreceptors in vivo. STOML3 inhibitors in the skin also reversibly attenuate fine touch perception in normal mice. Under pathophysiological conditions following nerve injury or diabetic neuropathy, the slightest touch can produce pain, and here STOML3 inhibitors can reverse mechanical hypersensitivity. Thus, small molecules applied locally to the skin can be used to modulate touch and may represent peripherally available drugs to treat tactile-driven pain following neuropathy.
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Piezo2 is the major transducer of mechanical forces for touch sensation in mice
Nature, 2014Co-Authors: Sanjeev S. Ranade, Rabih Moshourab, Seung-hyun Woo, Adrienne E. Dubin, Christiane Wetzel, Matt Petrus, Jayanti Mathur, Valérie Bégay, Bertrand Coste, James Kevin MainquistAbstract:The sense of touch provides critical information about our physical environment by transforming mechanical energy into electrical signals. It is postulated that mechanically activated cation channels initiate touch sensation, but the identity of these molecules in mammals has been elusive. Piezo2 is a rapidly adapting, mechanically activated ion channel expressed in a subset of sensory neurons of the dorsal root ganglion and in cutaneous Mechanoreceptors known as Merkel-cell-neurite complexes. It has been demonstrated that Merkel cells have a role in vertebrate mechanosensation using Piezo2, particularly in shaping the type of current sent by the innervating sensory neuron; however, major aspects of touch sensation remain intact without Merkel cell activity. Here we show that mice lacking Piezo2 in both adult sensory neurons and Merkel cells exhibit a profound loss of touch sensation. We precisely localize Piezo2 to the peripheral endings of a broad range of low-threshold Mechanoreceptors that innervate both hairy and glabrous skin. Most rapidly adapting, mechanically activated currents in dorsal root ganglion neuronal cultures are absent in Piezo2 conditional knockout mice, and ex vivo skin nerve preparation studies show that the mechanosensitivity of low-threshold Mechanoreceptors strongly depends on Piezo2. This cellular phenotype correlates with an unprecedented behavioural phenotype: an almost complete deficit in light-touch sensation in multiple behavioural assays, without affecting other somatosensory functions. Our results highlight that a single ion channel that displays rapidly adapting, mechanically activated currents in vitro is responsible for the mechanosensitivity of most low-threshold mechanoreceptor subtypes involved in innocuous touch sensation. Notably, we find that touch and pain sensation are separable, suggesting that as-yet-unknown mechanically activated ion channel(s) must account for noxious (painful) mechanosensation.
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kcnq4 k channels tune Mechanoreceptors for normal touch sensation in mouse and man
Nature Neuroscience, 2012Co-Authors: Matthias Heidenreich, Thomas J. Jentsch, Christiane Wetzel, Stefan G. Lechner, Vitya Vardanyan, Cor W. R. J. Cremers, Els De Leenheer, Gracia Aránguez, M A Morenopelayo, Gary R LewinAbstract:Mutations inactivating the potassium channel KCNQ4 (K(v)7.4) lead to deafness in humans and mice. In addition to its expression in mechanosensitive hair cells of the inner ear, KCNQ4 is found in the auditory pathway and in trigeminal nuclei that convey somatosensory information. We have now detected KCNQ4 in the peripheral nerve endings of cutaneous rapidly adapting hair follicle and Meissner corpuscle Mechanoreceptors from mice and humans. Electrophysiological recordings from single afferents from Kcnq4(-/-) mice and mice carrying a KCNQ4 mutation found in DFNA2-type monogenic dominant human hearing loss showed elevated mechanosensitivity and altered frequency response of rapidly adapting, but not of slowly adapting nor of D-hair, mechanoreceptor neurons. Human subjects from independent DFNA2 pedigrees outperformed age-matched control subjects when tested for vibrotactile acuity at low frequencies. This work describes a gene mutation that modulates touch sensitivity in mice and humans and establishes KCNQ4 as a specific molecular marker for rapidly adapting Meissner and a subset of hair follicle afferents.
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KCNQ4 K(+) channels tune Mechanoreceptors for normal touch sensation in mouse and man.
Nature neuroscience, 2011Co-Authors: Matthias Heidenreich, Christiane Wetzel, Stefan G. Lechner, Vitya Vardanyan, Cor W. R. J. Cremers, Els De Leenheer, Gracia Aránguez, M A Moreno-pelayo, Gary R LewinAbstract:Mutations inactivating the potassium channel KCNQ4 (K(v)7.4) lead to deafness in humans and mice. In addition to its expression in mechanosensitive hair cells of the inner ear, KCNQ4 is found in the auditory pathway and in trigeminal nuclei that convey somatosensory information. We have now detected KCNQ4 in the peripheral nerve endings of cutaneous rapidly adapting hair follicle and Meissner corpuscle Mechanoreceptors from mice and humans. Electrophysiological recordings from single afferents from Kcnq4(-/-) mice and mice carrying a KCNQ4 mutation found in DFNA2-type monogenic dominant human hearing loss showed elevated mechanosensitivity and altered frequency response of rapidly adapting, but not of slowly adapting nor of D-hair, mechanoreceptor neurons. Human subjects from independent DFNA2 pedigrees outperformed age-matched control subjects when tested for vibrotactile acuity at low frequencies. This work describes a gene mutation that modulates touch sensitivity in mice and humans and establishes KCNQ4 as a specific molecular marker for rapidly adapting Meissner and a subset of hair follicle afferents.
Mariane G Delaunay - One of the best experts on this subject based on the ideXlab platform.
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anatomy of avian rictal bristles in caprimulgiformes reveals reduced tactile function in open habitat partially diurnal foraging species
Journal of Anatomy, 2020Co-Authors: Mariane G Delaunay, Carl Larsen, Huw Lloyd, Matthew Sullivan, Robyn A GrantAbstract:: Avian rictal bristles are present in many species of birds, especially in nocturnal species. Rictal bristles occur along the upper beak and are morphologically similar to mammalian whiskers. Mammalian whiskers are important tactile sensors, guiding locomotion, foraging and social interactions, and have a well-characterised anatomy. However, it is not yet known whether avian rictal bristles have a sensory function, and their morphology, anatomy and function have also not been described in many species. Our study compares bristle morphology, follicle anatomy and their association with foraging traits, across 12 Caprimulgiform species. Rictal bristle morphology and follicle anatomy were diverse across the 12 species. Nine of the 12 species had Mechanoreceptors around their bristle follicles; however, there was large variation in their musculature, mechanoreceptor numbers and bristle morphology. Overall, species with short, thin, branching bristles that lacked Mechanoreceptors tended to forage pre-dusk in open habitats, whereas species with Mechanoreceptors around their bristle follicle tended to forage at night and in more closed habitats. We suggest that rictal bristles are likely to be tactile in many species and may aid in navigation, foraging and collision avoidance; however, identifying rictal bristle function is challenging and demands further investigation in many species.
Simon J Archibald - One of the best experts on this subject based on the ideXlab platform.
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f29 recovery of sensory modalities after peripheral nerve lesions associated with mechanoreceptor and sensory nerve fiber function
Clinical Neurophysiology, 2018Co-Authors: Christian Krarup, Birgitta Rosen, Michel E H Boeckstyns, Allan Ibsen Sorensen, Goran Lundborg, Mihai Moldovan, Simon J ArchibaldAbstract:Introduction Sensation is essential for recovery after peripheral nerve injury. However, the relationship between sensory modalities and function of regenerated fibers and reinnervated sensory receptors is uncertain. We have investigated the relationships between touch threshold, tactile gnosis and mechanoreceptor and sensory fiber function after nerve regeneration. Methods Twenty-one median or ulnar nerve lesions were repaired by a collagen nerve conduit or direct suture. Quantitative sensory hand function using a modified Rosen score and sensory conduction studies by near-nerve needle technique including tactile stimulation of Mechanoreceptors were followed for 2 years, and results were compared to non-injured hands. Results At both repair methods, touch thresholds at the finger tips recovered to 81 ± 3% whereas tactile gnosis only recovered to 20 ± 4% (P Conclusion The recovered function of regenerated peripheral nerve fibers and reinnervated Mechanoreceptors may differentially influence recovery of sensory modalities. Touch was affected by the number and function of regenerated fibers and Mechanoreceptors. In contrast, tactile gnosis depends on the input and plasticity of the CNS, which may explain the absence of a direct relation between electrophysiological parameters and poor recovery. Dispersed maturation of sensory nerve fibers with desynchronized inputs to the CNS also contributes to the poor recovery of tactile gnosis.
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sensation mechanoreceptor and nerve fiber function after nerve regeneration
Annals of Neurology, 2017Co-Authors: Christian Krarup, Birgitta Rosen, Michel E H Boeckstyns, Allan Ibsen Sorensen, Goran Lundborg, Mihai Moldovan, Simon J ArchibaldAbstract:Objective: Sensation is essential for recovery after peripheral nerve injury. However, the relationship between sensory modalities and function of regenerated fibers is uncertain. We have investigated the relationships between touch threshold, tactile gnosis, and mechanoreceptor and sensory fiber function after nerve regeneration. Methods: Twenty-one median or ulnar nerve lesions were repaired by a collagen nerve conduit or direct suture. Quantitative sensory hand function and sensory conduction studies by near-nerve technique, including tactile stimulation of Mechanoreceptors, were followed for 2 years, and results were compared to noninjured hands. Results: At both repair methods, touch thresholds at the finger tips recovered to 81 ± 3% and tactile gnosis only to 20 ± 4% (p < 0.001) of control. The sensory nerve action potentials (SNAPs) remained dispersed and areas recovered to 23 ± 2% and the amplitudes only to 7 ± 1% (P < 0.001). The areas of SNAPs after tactile stimulation recovered to 61 ± 11% and remained slowed. Touch sensation correlated with SNAP areas (p < 0.005) and was negatively related to the prolongation of tactile latencies (p < 0.01); tactile gnosis was not related to electrophysiological parameters. Interpretation: The recovered function of regenerated peripheral nerve fibers and reinnervated Mechanoreceptors may differentially influence recovery of sensory modalities. Touch was affected by the number and function of regenerated fibers and Mechanoreceptors. In contrast, tactile gnosis depends on the input and plasticity of the central nervous system (CNS), which may explain the absence of a direct relation between electrophysiological parameters and poor recovery. Dispersed maturation of sensory nerve fibers with desynchronized inputs to the CNS also contributes to the poor recovery of tactile gnosis. Ann Neurol 2017. Ann Neurol 2017;82:940–950. (Less)