-
Nature Reviews. Neuroscience Sep 2021Our sense of touch emerges from an array of mechanosensory structures residing within the fabric of our skin. These tactile end organ structures convert innocuous forces... (Review)
Review
Our sense of touch emerges from an array of mechanosensory structures residing within the fabric of our skin. These tactile end organ structures convert innocuous forces acting on the skin into electrical signals that propagate to the CNS via the axons of low-threshold mechanoreceptors (LTMRs). Our rich capacity for tactile discrimination arises from the dissimilar intrinsic properties of the LTMR subtypes that innervate different regions of the skin and the structurally distinct end organ complexes with which they associate. These end organ structures comprise a range of non-neuronal cell types, which may themselves actively contribute to the transformation of tactile forces into neural impulses within the LTMR afferents. Although the mechanism and the site of transduction across end organs remain unclear, PIEZO2 has emerged as the principal mechanosensitive channel involved in light touch of the skin. Here we review the physiological properties of LTMR subtypes and discuss how features of their cutaneous end organ complexes shape subtype-specific tuning.
Topics: Animals; Humans; Mechanoreceptors; Skin; Touch
PubMed: 34312536
DOI: 10.1038/s41583-021-00489-x -
Science (New York, N.Y.) Aug 2023Despite the potential importance of genital mechanosensation for sexual reproduction, little is known about how perineal touch influences mating. We explored how...
Despite the potential importance of genital mechanosensation for sexual reproduction, little is known about how perineal touch influences mating. We explored how mechanosensation affords exquisite awareness of the genitals and controls reproduction in mice and humans. Using genetic strategies and in vivo functional imaging, we demonstrated that the mechanosensitive ion channel PIEZO2 (piezo-type mechanosensitive ion channel component 2) is necessary for behavioral sensitivity to perineal touch. PIEZO2 function is needed for triggering a touch-evoked erection reflex and successful mating in both male and female mice. Humans with complete loss of PIEZO2 function have genital hyposensitivity and experience no direct pleasure from gentle touch or vibration. Together, our results help explain how perineal mechanoreceptors detect the gentlest of stimuli and trigger physiologically important sexual responses, thus providing a platform for exploring the sensory basis of sexual pleasure and its relationship to affective touch.
Topics: Animals; Female; Humans; Male; Mice; Ion Channels; Mechanoreceptors; Touch Perception; Penile Erection; Sexual Behavior
PubMed: 37616369
DOI: 10.1126/science.adg0144 -
Cell Aug 2023The properties of dorsal root ganglia (DRG) neurons that innervate the distal colon are poorly defined, hindering our understanding of their roles in normal physiology...
The properties of dorsal root ganglia (DRG) neurons that innervate the distal colon are poorly defined, hindering our understanding of their roles in normal physiology and gastrointestinal (GI) disease. Here, we report genetically defined subsets of colon-innervating DRG neurons with diverse morphologic and physiologic properties. Four colon-innervating DRG neuron populations are mechanosensitive and exhibit distinct force thresholds to colon distension. The highest threshold population, selectively labeled using Bmpr1b genetic tools, is necessary and sufficient for behavioral responses to high colon distension, which is partly mediated by the mechanosensory ion channel Piezo2. This Aδ-HTMR population mediates behavioral over-reactivity to colon distension caused by inflammation in a model of inflammatory bowel disease. Thus, like cutaneous DRG mechanoreceptor populations, colon-innervating mechanoreceptors exhibit distinct anatomical and physiological properties and tile force threshold space, and genetically defined colon-innervating HTMRs mediate pathophysiological responses to colon distension, revealing a target population for therapeutic intervention.
Topics: Ganglia, Spinal; Mechanoreceptors; Colon; Neurons; Skin
PubMed: 37541195
DOI: 10.1016/j.cell.2023.07.007 -
Cell Jan 2017The deep dorsal horn is a poorly characterized spinal cord region implicated in processing low-threshold mechanoreceptor (LTMR) information. We report an array of mouse...
The deep dorsal horn is a poorly characterized spinal cord region implicated in processing low-threshold mechanoreceptor (LTMR) information. We report an array of mouse genetic tools for defining neuronal components and functions of the dorsal horn LTMR-recipient zone (LTMR-RZ), a role for LTMR-RZ processing in tactile perception, and the basic logic of LTMR-RZ organization. We found an unexpectedly high degree of neuronal diversity in the LTMR-RZ: seven excitatory and four inhibitory subtypes of interneurons exhibiting unique morphological, physiological, and synaptic properties. Remarkably, LTMRs form synapses on between four and 11 LTMR-RZ interneuron subtypes, while each LTMR-RZ interneuron subtype samples inputs from at least one to three LTMR classes, as well as spinal cord interneurons and corticospinal neurons. Thus, the LTMR-RZ is a somatosensory processing region endowed with a neuronal complexity that rivals the retina and functions to pattern the activity of ascending touch pathways that underlie tactile perception.
Topics: Animals; Axons; Dendrites; Interneurons; Mechanoreceptors; Mice; Molecular Biology; Neural Pathways; Spinal Cord; Synapses; Touch Perception
PubMed: 28041852
DOI: 10.1016/j.cell.2016.12.010 -
Neuron Oct 2023Across mammalian skin, structurally complex and diverse mechanosensory end organs respond to mechanical stimuli and enable our perception of dynamic, light touch. How...
Across mammalian skin, structurally complex and diverse mechanosensory end organs respond to mechanical stimuli and enable our perception of dynamic, light touch. How forces act on morphologically dissimilar mechanosensory end organs of the skin to gate the requisite mechanotransduction channel Piezo2 and excite mechanosensory neurons is not understood. Here, we report high-resolution reconstructions of the hair follicle lanceolate complex, Meissner corpuscle, and Pacinian corpuscle and the subcellular distribution of Piezo2 within them. Across all three end organs, Piezo2 is restricted to the sensory axon membrane, including axon protrusions that extend from the axon body. These protrusions, which are numerous and elaborate extensively within the end organs, tether the axon to resident non-neuronal cells via adherens junctions. These findings support a unified model for dynamic touch in which mechanical stimuli stretch hundreds to thousands of axon protrusions across an end organ, opening proximal, axonal Piezo2 channels and exciting the neuron.
Topics: Animals; Merkel Cells; Mechanotransduction, Cellular; Imaging, Three-Dimensional; Ion Channels; Mechanoreceptors; Mammals
PubMed: 37725982
DOI: 10.1016/j.neuron.2023.08.023 -
Cell Research Jan 2016Sensory neurons are distinguished by distinct signaling networks and receptive characteristics. Thus, sensory neuron types can be defined by linking transcriptome-based...
Sensory neurons are distinguished by distinct signaling networks and receptive characteristics. Thus, sensory neuron types can be defined by linking transcriptome-based neuron typing with the sensory phenotypes. Here we classify somatosensory neurons of the mouse dorsal root ganglion (DRG) by high-coverage single-cell RNA-sequencing (10 950 ± 1 218 genes per neuron) and neuron size-based hierarchical clustering. Moreover, single DRG neurons responding to cutaneous stimuli are recorded using an in vivo whole-cell patch clamp technique and classified by neuron-type genetic markers. Small diameter DRG neurons are classified into one type of low-threshold mechanoreceptor and five types of mechanoheat nociceptors (MHNs). Each of the MHN types is further categorized into two subtypes. Large DRG neurons are categorized into four types, including neurexophilin 1-expressing MHNs and mechanical nociceptors (MNs) expressing BAI1-associated protein 2-like 1 (Baiap2l1). Mechanoreceptors expressing trafficking protein particle complex 3-like and Baiap2l1-marked MNs are subdivided into two subtypes each. These results provide a new system for cataloging somatosensory neurons and their transcriptome databases.
Topics: Animals; Base Sequence; Cells, Cultured; Ganglia, Spinal; Gene Regulatory Networks; Male; Mechanoreceptors; Mice; Mice, Inbred C57BL; Multigene Family; Nociceptors; Patch-Clamp Techniques; Sensory Receptor Cells; Sequence Analysis, RNA; Transcriptome
PubMed: 26691752
DOI: 10.1038/cr.2015.149 -
Annual Review of Physiology Feb 2018Bacteria represent one of the most evolutionarily successful groups of organisms to inhabit Earth. Their world is awash with mechanical cues, probably the most ancient... (Review)
Review
Bacteria represent one of the most evolutionarily successful groups of organisms to inhabit Earth. Their world is awash with mechanical cues, probably the most ancient form of which are osmotic forces. As a result, they have developed highly robust mechanosensors in the form of bacterial mechanosensitive (MS) channels. These channels are essential in osmoregulation, and in this setting, provide one of the simplest paradigms for the study of mechanosensory transduction. We explore the past, present, and future of bacterial MS channels, including the alternate mechanosensory roles that they may play in complex microbial communities. Central to all of these functions is their ability to change conformation in response to mechanical stimuli. We discuss their gating according to the force-from-lipids principle and its applicability to eukaryotic MS channels. This includes the new paradigms emerging for bilayer-mediated channel mechanosensitivity and how this molecular detail may provide advances in both industry and medicine.
Topics: Bacteria; Bacterial Proteins; Cell Membrane; Ion Channels; Mechanoreceptors; Mechanotransduction, Cellular; Osmoregulation
PubMed: 29195054
DOI: 10.1146/annurev-physiol-021317-121351 -
Nature Dec 2014The sense of touch provides critical information about our physical environment by transforming mechanical energy into electrical signals. It is postulated that...
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.
Topics: Animals; Ion Channels; Mechanoreceptors; Mechanotransduction, Cellular; Merkel Cells; Mice; Mice, Knockout; Sensory Receptor Cells; Skin; Touch
PubMed: 25471886
DOI: 10.1038/nature13980 -
The Journal of Physiology May 2022
Topics: Mechanoreceptors; Muscle Spindles; Proprioception; Vibration
PubMed: 35114007
DOI: 10.1113/JP282865 -
The Journal of Physiology Jul 2022
Topics: Mechanoreceptors; Skin; Touch Perception
PubMed: 35366337
DOI: 10.1113/JP282866