The mechanosensory neurons of touch and their mechanisms of activation

Handler, Annie; Ginty, David D.

doi:10.1038/s41583-021-00489-x

Cited by 233 publications

(244 citation statements)

References 167 publications

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“…Although affective social touch begins at the skin’s surface, the molecular identity of sensory neurons in the skin that detect socially relevant signals and pass them to the central nervous system has remained unknown. Moreover, because touch itself is highly heterogeneous (i.e., discriminative touch to detect texture with our fingertips versus the affiliative touch during a hug from a friend), sensory perception is likely generated by different sets of neurons to provide specificity (Handler and Ginty, 2021; Li et al, 2011; Maksimovic et al, 2014; Neubarth et al, 2020; Rodgers et al, 2021; Seal et al, 2009b; Severson et al, 2017; Sharma et al, 2020). Armed with this information, where does one begin the search for touch neurons underlying social reward, including sexual receptivity?…”

Section: Discussionmentioning

confidence: 99%

“…A class of sensory neurons in humans that are linked to gentle stroking are termed C-tactile afferents (Ackerley et al, 2014; Pawling et al, 2017), and there are putative populations of these neurons in the mouse (Delfini et al, 2013; Handler and Ginty, 2021; Lou et al, 2013). One such class of neurons in mice express the G-protein coupled receptor Mrgprb4 and appear to share anatomical and physiological similarities with human C-tactile afferents (Liu et al, 2007; Vrontou et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Identification of touch neurons underlying dopaminergic pleasurable touch and sexual receptivity

Middleton¹,

Schaffler

Succi

et al. 2021

Preprint

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Pleasurable touch during social behavior is the key to building familial bonds and meaningful connections. One form of social touch occurs during sex. Although sexual behavior is initiated in part by touch, and touch is ongoing throughout copulation, the identity and role of sensory neurons that transduce sexual touch remain completely unknown. A population of sensory neurons labeled by the G-protein coupled receptor Mrgprb4 detect stroking touch in mice. Here, we study the social relevance of this population by genetically engineering mice to allow activation or ablation of Mrgprb4-lineage neurons and reveal that these neurons are required for sexual receptivity and sufficient to activate reward circuitry. Even in social isolation, optogenetic stimulation of Mrgprb4-lineage neurons through the back skin is sufficient to induce a conditioned place preference and a striking lordosis-like copulatory posture in females. In the absence of Mrgprb4-lineage neurons, female mice no longer find male mounts rewarding: sexual receptivity is supplanted by aggression and a coincident decline in dopaminergic release in the mesolimbic reward pathway. In addition to sexual behavior, Mrgprb4-lineage neurons are also required for social postures induced by female-to-female back touch. Together, these findings reveal a skin-to-brain circuit encoding the rewarding quality of social touch.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of touch neurons underlying dopaminergic pleasurable touch and sexual receptivity

Middleton¹,

Schaffler

Succi

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Apart from low-threshold mechanoreceptive (LTM) Aβ-fibres that all express PIEZO2, this expression in LTM C-fibres has not safely been established [ 66 ]. These slowly adapting fibres have been shown to contribute to tactile allodynia in mouse models of inflammation, nerve injury, and trauma [ 56 , 152 ].…”

Section: Piezo2 and Painmentioning

confidence: 99%

Nobel somatosensations and pain

Reeh

Fischer

2022

Pflugers Arch - Eur J Physiol

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The Nobel prices 2021 for Physiology and Medicine have been awarded to David Julius and Ardem Patapoutian "for their discoveries of receptors for temperature and touch", TRPV1 and PIEZO1/2. The present review tells the past history of the capsaicin receptor, covers further selected TRP channels, TRPA1 in particular, and deals with mechanosensitivity in general and mechanical hyperalgesia in particular. Other achievements of the laureates and translational aspects of their work are shortly treated.

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“…In the spinal dorsal horn, nociceptive and tactile mechanosensory information are transmitted to separate circuits comprising projection neurons and local interneurons [57][58][59] . Under normal conditions, an innocuous touch activates mechanosensory inputs via myelinated Aδ and Aβ fibers as well as unmyelinated C fibers, thereby exciting mechanosensory projection neurons and generating a touch sensation 60,61 . Normally, the flow of sensory information from Aβ fibers to nociceptive circuits is blocked by local inhibitory interneurons that potently inhibit excitatory interneurons, such as somatostatin-expressing interneurons, and additionally suppress presynaptic sensory terminals, thus preventing activation of nociceptive projection neurons and ascending nociceptive pathway by tactile sensory inputs under normal conditions.…”

Section: Discussionmentioning

confidence: 99%

Spinal cord homeostatic plasticity gates mechanical allodynia in chronic pain

Cao

Scherrer

Chen

2022

Preprint

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Central sensitization caused by disinhibition of spinal cord circuits is a key mechanism of mechanical allodynia in neuropathic pain. Despite intense efforts, the molecular mechanisms that drive disinhibition and induce allodynia after peripheral nerve injury remain unclear. Using the spared-nerve injury (SNI) model of allodynia, we here demonstrate that SNI induces disinhibition of spinal nociceptive circuits by triggering homeostatic synaptic plasticity. Specifically, SNI-triggered homeostatic plasticity suppresses the inhibitory outputs of parvalbumin-positive (PV+) interneurons that form synapses on both primary afferent terminals and excitatory interneurons, causing hyperactivation of the nociceptive pathway. Using genetic manipulations, we identified the retinoic acid receptor RARα as the key mediator of the homeostatic synaptic plasticity underlying this synaptic disinhibition. Deletion of RARα in PV+ neurons blocked SNI-induced spinal disinhibition, central sensitization, and allodynia. Moreover, deletion of RARα in spinal PV+ neurons or application of an RARα antagonist in the spinal cord prevented the development of SNI-induced mechanical allodynia. Together, our results reveal a molecular mechanism of neuropathic pain whereby homeostatic plasticity causes the mis-direction of tactile information flow to ascending nociceptive pathways following peripheral nerve injury.

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The mechanosensory neurons of touch and their mechanisms of activation

Cited by 233 publications

References 167 publications

Identification of touch neurons underlying dopaminergic pleasurable touch and sexual receptivity

Identification of touch neurons underlying dopaminergic pleasurable touch and sexual receptivity

Nobel somatosensations and pain

Spinal cord homeostatic plasticity gates mechanical allodynia in chronic pain

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