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

Abstract

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...

Dissection of Merkel cell formation in hairy and glabrous skin reveals a common requirement for FGFR2‐mediated signalling

“…Future studies on the morphogenesis of Merkel cells are important not only for our understanding of the biology of the skin as a sensory organ but also for uncovering processes that lead to human pathologies. Hyper‐ or hypo‐sensitivity to touch have long been reported in patients with diabetes, inflammation or autism . Recent studies have shown that Merkel cells can inhibit alloknesis, a disease state where mechanical light touch stimuli provoke itching .…”

“…Hyper-or hypo-sensitivity to touch have long been reported in patients with diabetes, inflammation or autism. [33][34][35][36] Recent studies have shown that Merkel cells can inhibit alloknesis, a disease state where mechanical light touch stimuli provoke itching. [37] Finally, these discoveries might help us uncover which mechanisms control Merkel cell carcinoma, a deadly skin disease with no effective treatment.…”

Active Touch and Self-Motion Encoding by Merkel Cell-Associated Afferents

“…In the fingertip and hairy skin, decades of work have characterized responses of slowly adapting (SA) type 1 afferents, which correspond to large-diameter nerve fibers that associate with Merkel cells in the skin (Iggo and Muir, 1969; Woodbury and Koerber, 2007). Recent work has shown that mechanical activation of Piezo channels drives spiking in both Merkel cells and their afferents (Ikeda et al, 2014; Maksimovic et al, 2014; Ranade et al, 2014; Woo et al, 2014), and that Merkel cells synaptically excite their afferents (Chang et al, 2016; Maksimovic et al, 2014). …”

Electrophysiological property and chemical sensitivity of primary afferent neurons that innervate rat whisker hair follicles

“…Although metabotropic 5-HT receptors do not directly permit current flowing through, previous studies have shown that activation of 5-HT 2A/2C and 5-HT 7 receptors could elicit inward currents through the potentiation of I h currents (Tang and Trussell, 2015). We have recently shown in mouse whisker afferent neurons that serotonin evoke fast and slow currents by activating 5-HT 3 and 5-HT 2A/2B receptors, respectively (Chang et al., 2016). …”