Journal Article

Genetic identification of C fibres that detect massage-like stroking of hairy skin in vivo

Vrontou, Sophia, Koerber, H. Richard, Anderson, David J., Rau, Kristofer K., Wong, Allan M.

2013

Overview

Calcium imaging in live mice shows that a rare population of unmyelinated sensory neurons—expressing the G-protein-coupled receptor MRGPRB4—responds specifically to massage-like stroking of hairy skin, with positive reinforcing behavioural effects. 'Massage' neurons make it good to be stroked Pleasant stimulation of skin serves important social functions in mammals, but has received less attention from molecular neurobiologists than the response to noxious stimuli. Now David Anderson and colleagues have used calcium imaging in live mice to show that a small population of sensory neurons in hairy skin — expressing the G-protein-coupled receptor MRGPRB4 — responds specifically to strokes from a small paintbrush intended to simulate natural stroking or grooming, but not to pinching or poking stimuli, which activate a different population of sensory neurons expressing MRGPRD. Pharmacological stimulation of MRGPRB4 + neurons elicits positive reinforcing behavioural effects. The 'stroke-sensitive' neurons resemble C-tactile afferents, unmyelinated mechanoreceptive neurons found in hairy skin of humans and other mammals. The functional characterization of this novel population of neurons opens the way to identifying molecular transduction mechanisms and neural circuitry associated with a positive affective state — or pleasure. Stroking of the skin produces pleasant sensations that can occur during social interactions with conspecifics, such as grooming 1 . Despite numerous physiological studies (reviewed in ref. 2 ), molecularly defined sensory neurons that detect pleasant stroking of hairy skin 3 , 4 in vivo have not been reported. Previously, we identified a rare population of unmyelinated sensory neurons in mice that express the G-protein-coupled receptor MRGPRB4 (refs 5 , 6 ). These neurons exclusively innervate hairy skin with large terminal arborizations 7 that resemble the receptive fields of C-tactile (CT) afferents in humans 8 . Unlike other molecularly defined mechanosensory C-fibre subtypes 9 , 10 , MRGPRB4 + neurons could not be detectably activated by sensory stimulation of the skin ex vivo. Therefore, we developed a preparation for calcium imaging in the spinal projections of these neurons during stimulation of the periphery in intact mice. Here we show that MRGPRB4 + neurons are activated by massage-like stroking of hairy skin, but not by noxious punctate mechanical stimulation. By contrast, a different population of C fibres expressing MRGPRD 11 was activated by pinching but not by stroking, consistent with previous physiological and behavioural data 10 , 12 . Pharmacogenetic activation of Mrgprb4- expressing neurons in freely behaving mice promoted conditioned place preference 13 , indicating that such activation is positively reinforcing and/or anxiolytic. These data open the way to understanding the function of MRGPRB4 neurons during natural behaviours, and provide a general approach to the functional characterization of genetically identified subsets of somatosensory neurons in vivo .

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/378/340 / Animals / Cell receptors / Conspecifics / Experiments / Fibers / Gene Expression Profiling / Genetic aspects / Genetic screening / Hair follicles / Humanities and Social Sciences / letter / Medical research / Methods / Mice / multidisciplinary / Nerve Fibers, Unmyelinated - metabolism / Nerves / Neurons / Physiological aspects / Physiology / Properties / Receptors, G-Protein-Coupled - genetics / Receptors, G-Protein-Coupled - metabolism / Rodents / Science / Sensory Receptor Cells - metabolism / Skin / Skin - innervation / Social behavior / Spinal cord / Touch - genetics