Neurotransmitters and synaptic components in the Merkel cell–neurite complex, a gentle‐touch receptor

Maksimovic, Srdjan; Baba, Yoshichika; Lumpkin, Ellen A.

doi:10.1111/nyas.12057

Cited by 80 publications

(81 citation statements)

References 77 publications

(249 reference statements)

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“…paracrine to modify Merkel disc's functions (3,10,19) rather than to be transmitters to directly elicit tactile impulses at Aβ-afferent endings in Merkel discs. Thus, molecular mechanisms underlying tactile signaling at Merkel discs remain largely obscured.…”

Section: Significancementioning

confidence: 99%

“…It has been hypothesized that Merkel discs may be sensory synapses and tactile signals are transmitted synaptically from MCs to Aβ-afferent nerve endings (3,9,10). However, it has long been believed that the first sensory synapses for somatosensory signals are located centrally in the dorsal horn of the spinal cord and brainstem, where sensory signals are transmitted synaptically using glutamate (Glu) as a principal neurotransmitter (11,12).…”

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confidence: 99%

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

Chang

Kanda

Ikeda

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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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.Merkel cells | touch | serotonin | 5-HT receptors | whisker hair follicles S ensory systems for detecting tactile stimuli have evolved from mechanosensitive free nerve endings in invertebrates to complicated tactile end organs in mammals, although mechanosensitive free nerve endings are conserved in mammals mainly for noxious mechanical stimuli. Tactile end organs, including Merkel discs, Pacinian corpuscles, Meissner's corpuscles, and Ruffini endings, are highly specialized structures in the periphery of mammals (1, 2). These organs are crucial to the performance of sophisticated sensory tasks, such as environmental explorations, social interactions, and tactile discrimination (2). The Merkel disc, also known as Merkel cell-neurite complex, is a main type of tactile end organ highly abundant in human fingertips, whisker hair follicles, touch domes, and other tactile-sensitive spots throughout mammalian bodies (3, 4). Structurally, Merkel discs are composed of Merkel cells (MCs) and their associated Aβ-afferent nerve endings to form a structure of disc-shaped expansion (3, 5). Merkel discs have high tactile acuity and are very sensitive to skin indentation, pressure, hair movement, and other tactile stimuli. Tactile stimuli to Merkel discs in the touch domes...

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Section: Significancementioning

confidence: 99%

mentioning

confidence: 99%

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

Chang

Kanda

Ikeda

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Due to the fact that tactile stimuli are directly received by afferent neurons in invertebrates, the role of Merkel cells in touch sensation has been debated (Chalfie, 2009;Lumpkin et al, 2010;Maksimovic et al, 2013;Maricich et al, 2012). Exciting recent studies in mammals, however, have shown that upon direct touch stimuli, Merkel cells display ionic currents that induce the release of neurotransmitters, which in turn trigger action potential firing of the Aβ-afferent fibers.…”

Section: Introductionmentioning

confidence: 99%

Embryonic maturation of epidermal Merkel cells is controlled by a redundant transcription factor network

et al. 2014

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Merkel cell-neurite complexes are located in touch-sensitive areas of the mammalian skin and are involved in recognition of the texture and shape of objects. Merkel cells are essential for these tactile discriminations, as they generate action potentials in response to touch stimuli and induce the firing of innervating afferent nerves. It has been shown that Merkel cells originate from epidermal stem cells, but the cellular and molecular mechanisms of their development are largely unknown. In this study, we analyzed Merkel cell differentiation during development and found that it is a temporally regulated maturation process characterized by a sequential activation of Merkel cell-specific genes. We uncovered key transcription factors controlling this process and showed that the transcription factor Atoh1 is required for initial Merkel cell specification. The subsequent maturation steps of Merkel cell differentiation are controlled by cooperative function of the transcription factors Sox2 and Isl1, which physically interact and work to sustain Atoh1 expression. These findings reveal the presence of a robust transcriptional network required to produce functional Merkel cells that are required for tactile discrimination.

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“…The response is maintained throughout the stimulus which allows these cells to distinguish two points of discrimination close together which includes texture. This is the process which identifies fine spatial details such as Braille‐like characters 24. The buccal region of the human has a sensory innervation well represented by Penfield's sensory homunculus.…”

Section: Early Instinctual Behaviour In Animals and Newborn Infantsmentioning

confidence: 99%

“…The oral tactile imprint is a learnt form of perceptual recognition via Merkel cell mechanosensation which governs the imprinting process 24. The baby's return to the nipple (‘mother in the mouth’) is an emotionally directed process termed ‘latchment’ 9.…”

Section: Early Instinctual Behaviour In Animals and Newborn Infantsmentioning

confidence: 99%

Imprinting, latchment and displacement: a mini review of early instinctual behaviour in newborn infants influencing breastfeeding success

Mobbs

Mobbs³

2015

Acta Paediatrica

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Instinctive behaviours have evolved favouring the mother–infant dyad based on fundamental processes of neurological development, including oral tactile imprinting and latchment. Latchment is the first stage of emotional development based on the successful achievement of biological imprinting. The mechanisms underpinning imprinting are identified and the evolutionary benefits discussed.ConclusionIt is proposed that the oral tactile imprint to the breast is a keystone for optimal latchment and breastfeeding, promoting evolutionary success.

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Neurotransmitters and synaptic components in the Merkel cell–neurite complex, a gentle‐touch receptor

Cited by 80 publications

References 77 publications

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

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

Embryonic maturation of epidermal Merkel cells is controlled by a redundant transcription factor network

Imprinting, latchment and displacement: a mini review of early instinctual behaviour in newborn infants influencing breastfeeding success

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