Merkel disc is a serotonergic synapse in the epidermis for transmitting tactile signals in mammals

The evolution of sensory systems has let mammals develop complicated tactile end organs to enable sophisticated sensory tasks, including social interaction, environmental exploration, and tactile discrimination. The Merkel disc, a main type of tactile end organ consisting of Merkel cells (MCs) and Aβ-afferent endings, are highly abundant in fingertips, touch domes, and whisker hair follicles of mammals. The Merkel disc has high tactile acuity for an object’s physical features, such as texture, shape, and edges. Mechanisms underlying the tactile function of Merkel discs are obscured as to how MCs transmit tactile signals to Aβ-afferent endings leading to tactile sensations. Using mouse whisker hair follicles, we show herein that tactile stimuli are transduced by MCs into excitatory signals that trigger vesicular serotonin release from MCs. We identify that both ionotropic and metabotropic 5-hydroxytryptamine (5-HT) receptors are expressed on whisker Aβ-afferent endings and that their activation by serotonin released from MCs initiates Aβ-afferent impulses. Moreover, we demonstrate that these ionotropic and metabotropic 5-HT receptors have a synergistic effect that is critical to both electrophysiological and behavioral tactile responses. These findings elucidate that the Merkel disc is a unique serotonergic synapse located in the epidermis and plays a key role in tactile transmission. The epidermal serotonergic synapse may have important clinical implications in sensory dysfunctions, such as the loss of tactile sensitivity and tactile allodynia seen in patients who have diabetes, inflammatory diseases, and undergo chemotherapy. It may also have implications in the exaggerated tactile sensations induced by recreational drugs that act on serotoninergic synapses.

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Effects on tactile transmission by serotonin transporter inhibitors at Merkel discs of mouse whisker hair follicles

Molecular Pain ◽

10.1177/1744806920938237 ◽

2020 ◽

Vol 16 ◽

pp. 174480692093823 ◽

Cited By ~ 1

Author(s):

Weipang Chang ◽

Jianguo G Gu

Keyword(s):

Serotonin Transporter ◽

Potent Inhibitor ◽

Serotonin Release ◽

Hair Follicles ◽

Prolonged Treatment ◽

Merkel Cells ◽

Serotonin Transporters ◽

Afferent Nerves ◽

Environmental Exploration

The Merkel disc is a main type of tactile end organs formed by Merkel cells and Aβ-afferent endings as first tactile sensory synapses. They are highly abundant in fingertips, touch domes, and whisker hair follicles of mammals and are essential for sensory tasks including social interaction, environmental exploration, and tactile discrimination. We have recently shown that Merkel discs use serotonin to transmit tactile signals from Merkel cells to Aβ-afferent endings to drive slowly adapting type 1 impulses on the Aβ-afferent nerves. This raises a question as whether the serotoninergic transmission at Merkel discs may be regulated by serotonin transporters and whether serotonin transporter inhibitors may affect the tactile transmission. Here, we made recordings from whisker afferent nerves of mouse whisker hair follicles and tested the effects of monoamine transporter inhibitors on slowly adapting type 1 impulses. We show that methamphetamine, a monoamine releasing facilitator and reuptake inhibitor, elicited spontaneous impulses as well as increased the numbers of slowly adapting type 1 impulses elicited by whisker hair deflections. S-duloxetine, a potent inhibitor of transporters of serotonin and norepinephrine, and fluoxetine, a selective inhibitor of serotonin transporters, both also increased the numbers of slowly adapting type 1 impulses. Prolonged treatment of whisker hair follicles with methamphetamine abolished most of slowly adapting type 1 impulses. Furthermore, the treatment of whisker hair follicles with methamphetamine resulted in serotonin release from whisker hair follicles. Taken together, our results suggest that serotonin transporters play a role in regulating tactile transmission at Merkel discs.

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Non-informative vision improves spatial tactile discrimination on the shoulder but does not influence detection sensitivity

Experimental Brain Research ◽

10.1007/s00221-020-05944-2 ◽

2020 ◽

Vol 238 (12) ◽

pp. 2865-2875

Author(s):

Fabrizio Leo ◽

Sara Nataletti ◽

Luca Brayda

Keyword(s):

Tactile Stimulation ◽

Detection Threshold ◽

Receptive Fields ◽

Judgment Task ◽

The Body ◽

Detection Sensitivity ◽

Body Parts ◽

Tactile Acuity ◽

Tactile Stimuli ◽

Numerosity Judgment

Abstract Vision of the body has been reported to improve tactile acuity even when vision is not informative about the actual tactile stimulation. However, it is currently unclear whether this effect is limited to body parts such as hand, forearm or foot that can be normally viewed, or it also generalizes to body locations, such as the shoulder, that are rarely before our own eyes. In this study, subjects consecutively performed a detection threshold task and a numerosity judgment task of tactile stimuli on the shoulder. Meanwhile, they watched either a real-time video showing their shoulder or simply a fixation cross as control condition. We show that non-informative vision improves tactile numerosity judgment which might involve tactile acuity, but not tactile sensitivity. Furthermore, the improvement in tactile accuracy modulated by vision seems to be due to an enhanced ability in discriminating the number of adjacent active electrodes. These results are consistent with the view that bimodal visuotactile neurons sharp tactile receptive fields in an early somatosensory map, probably via top-down modulation of lateral inhibition.

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Growth of Nerve Fibers to Merkel Cells Observed in Co-Culture of Sensory Ganglia and Sinus Hair Follicles

The Merkel Cell ◽

10.1007/978-3-662-10358-6_18 ◽

2003 ◽

pp. 113-120

Author(s):

Jun Fukuda ◽

Hisako Ishimine ◽

Kazuko Keino-Masu ◽

Yoshiaki Masaki

Keyword(s):

Nerve Fibers ◽

Hair Follicles ◽

Sensory Ganglia ◽

Merkel Cells

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Neuronal responses to tactile stimuli and tactile sensations evoked by microstimulation in the human thalamic principal somatic sensory nucleus (ventral caudal)

Journal of Neurophysiology ◽

10.1152/jn.00611.2015 ◽

2016 ◽

Vol 115 (5) ◽

pp. 2421-2433 ◽

Cited By ~ 8

Author(s):

Anne-Christine Schmid ◽

Jui-Hong Chien ◽

Joel D. Greenspan ◽

Ira Garonzik ◽

Nirit Weiss ◽

...

Keyword(s):

Spinal Cord ◽

Chronic Pain ◽

Nervous System ◽

Single Neuron ◽

The Body ◽

Neuronal Responses ◽

Tactile Stimuli ◽

Sensory Nucleus ◽

Tactile Sensations ◽

Sensory Abnormality

The normal organization and plasticity of the cutaneous core of the thalamic principal somatosensory nucleus (ventral caudal, Vc) have been studied by single-neuron recordings and microstimulation in patients undergoing awake stereotactic operations for essential tremor (ET) without apparent somatic sensory abnormality and in patients with dystonia or chronic pain secondary to major nervous system injury. In patients with ET, most Vc neurons responded to one of the four stimuli, each of which optimally activates one mechanoreceptor type. Sensations evoked by microstimulation were similar to those evoked by the optimal stimulus only among rapidly adapting neurons. In patients with ET, Vc was highly segmented somatotopically, and vibration, movement, pressure, and sharp sensations were usually evoked by microstimulation at separate sites in Vc. In patients with conditions including spinal cord transection, amputation, or dystonia, RFs were mismatched with projected fields more commonly than in patients with ET. The representation of the border of the anesthetic area (e.g., stump) or of the dystonic limb was much larger than that of the same part of the body in patients with ET. This review describes the organization and reorganization of human Vc neuronal activity in nervous system injury and dystonia and then proposes basic mechanisms.

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Dopamine Alters Tactile Perception in Parkinson's Disease

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100012683 ◽

2012 ◽

Vol 39 (1) ◽

pp. 52-57 ◽

Cited By ~ 15

Author(s):

Aimee J. Nelson ◽

Azra Premji ◽

Navjot Rai ◽

Tasnuva Hoque ◽

Mark Tommerdahl ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Temporal Order ◽

Temporal Order Judgment ◽

Tactile Perception ◽

Somatosensory Processing ◽

Motor Impairments ◽

Tactile Acuity ◽

Tactile Stimuli ◽

The Right

Background:Abnormal somatosensory processing may contribute to motor impairments observed in Parkinson's disease (PD). Dopaminergic medications have been shown to alter somatosensory processing such that tactile perception is improved. In PD, it remains unclear whether the temporal sequencing of tactile stimuli is altered and if dopaminergic medications alter this perception.Methods:Somatosensory tactile perception was investigated using temporal order judgment in patients with Parkinson's disease on and off dopaminergic medications and in aged-matched healthy controls. Measures of temporal order judgment were acquired using computer controlled stimulation to digits 2 and 3 on the right hand and subjects were required to determine which stimuli occurred first. Two experimental tasks were compared, temporal order judgment without and with synchronization whereby digits 2 and 3 were vibrated synchronously in advance of the temporal order judgment sequence of stimuli.Results:Temporal order judgment in PD patients off and on medications were similar to controls. Temporal order judgment preceded by synchronous vibration impaired tactile acuity in controls and in PD off medications to similar degrees, but this perceptual impairment by synchronous vibration was not present in PD patients on medications.Conclusions:These findings suggest that dopamine in PD reduces cortico-cortical connectivity within SI and this leads to changes in tactile sensitivity.

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Chondroid Syringoma

Archives of Pathology & Laboratory Medicine ◽

10.5858/2004-128-986-cs ◽

2004 ◽

Vol 128 (9) ◽

pp. 986-990 ◽

Cited By ~ 1

Author(s):

Mohamed E. Salama ◽

Muhammad Azam ◽

Chan K. Ma ◽

Adrian Ormsby ◽

Richard J. Zarbo ◽

...

Keyword(s):

Neck Region ◽

Hair Follicles ◽

Follicular Epithelium ◽

Merkel Cells ◽

Chondroid Syringoma ◽

Significant Difference ◽

Normal Hair ◽

Henry Ford ◽

Adnexal Tumor ◽

Normal Epidermis

Abstract Context.—Chondroid syringoma (CS) is a benign cutaneous adnexal tumor with epithelial and stromal components. Epithelial components derived from folliculo-sebaceous-apocrine germ are evident in apocrine but not in eccrine CS. Objectives.—To further characterize pilosebaceous differentiation and to identify the presence of Merkel cells in the areas of follicular differentiation. Design.—Histologic type, folliculo-sebaceous differentiation, character of stroma, and presence or absence of Merkel cells by cytokeratin (CK) 20 immunoreactivity were evaluated in 25 CSs (22 apocrine and 3 eccrine) from the surgical pathology files of Henry Ford Hospital (Detroit, Mich). Results.—Most CSs occurred in the head and neck region of patients aged 40 years or older. We found no significant difference in sex, age, or location between apocrine and eccrine types. The stroma varied from myxoid (100%) to chondroid (59%), with various amounts of fat (59%) and ossification identified in 2 cases (9%) of apocrine type, but was homogeneously myxoid in the eccrine type. Follicular and sebaceous differentiation was found in 64% and 32% of apocrine CSs, respectively. Only 2 (14%) apocrine CSs with follicular differentiation were positive for CK20 (a few scattered cells in one case and numerous grouped cells in the other in association with follicular epithelium). No correlation was found between type of stroma and the presence of Merkel cells. Scattered Merkel cells were identified in 83% of normal hair follicles and in 33.3% of normal epidermis. Conclusion.—A high proportion of apocrine CSs show folliculo-sebaceous differentiation. The presence of Merkel cells in foci of follicular differentiation of CS supports the hypothesis that Merkel cells may be an integral constituent of follicles. To our knowledge, the presence of Merkel cells in CS, particularly in proliferative form, has not been described previously in the literature.

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Merkel Cells Transduce and Encode Tactile Stimuli to Drive Aβ-Afferent Impulses

Cell ◽

10.1016/j.cell.2014.02.026 ◽

2014 ◽

Vol 157 (3) ◽

pp. 664-675 ◽

Cited By ~ 147

Author(s):

Ryo Ikeda ◽

Myeounghoon Cha ◽

Jennifer Ling ◽

Zhanfeng Jia ◽

Dennis Coyle ◽

...

Keyword(s):

Merkel Cells ◽

Tactile Stimuli

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The Effect of Visual and Auditory Information on the Perception of Pleasantness and Roughness of Virtual Surfaces

Multisensory Research ◽

10.1163/22134808-00002603 ◽

2018 ◽

Vol 31 (6) ◽

pp. 501-522 ◽

Cited By ~ 3

Author(s):

Roberta Etzi ◽

Francesco Ferrise ◽

Monica Bordegoni ◽

Massimiliano Zampini ◽

Alberto Gallace

Keyword(s):

Haptic Perception ◽

Haptic Device ◽

Auditory Information ◽

Glass Plastic ◽

Haptic Exploration ◽

Tactile Stimuli ◽

Sensory Modalities ◽

Hedonic Evaluation ◽

Frictional Coefficients ◽

Tactile Sensations

Despite the large number of studies on the multisensory aspects of tactile perception, very little is known regarding the effects of visual and auditory sensory modalities on the tactile hedonic evaluation of textures, especially when the presentation of the stimuli is mediated by a haptic device. In this study, different haptic virtual surfaces were rendered by varying the static and dynamic frictional coefficients of a Geomagic® Touch device. In Experiment 1, the haptic surfaces were paired with pictures representing everyday materials (glass, plastic, rubber and steel); in Experiment 2, the haptic surfaces were paired with sounds resulting from the haptic exploration of paper or sandpaper. In both the experiments, participants were required to rate the pleasantness and the roughness of the virtual surfaces explored. Exploration times were also recorded. Both pleasantness and roughness judgments, as well as the durations of exploration, varied as a function of the combinations of the visuo-tactile and the audio-tactile stimuli presented. Taken together, these results suggest that vision and audition modulate haptic perception and hedonic preferences when tactile sensations are provided through a haptic device. Importantly, these results offer interesting suggestions for designing more pleasant, and even more realistic, multisensory virtual surfaces.

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