{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T09:42:58Z","timestamp":1769938978257,"version":"3.49.0"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>C\u2010low threshold mechanoreceptors (C\u2010LTMRs) in animals (termed C\u2010tactile (CT) fibres in humans) are a subgroup of C\u2010fibre primary afferents, which innervate hairy skin and respond to low\u2010threshold punctate indentations and brush stimuli. These afferents respond to gentle touch stimuli and are implicated in mediating pleasant\/affective touch. These afferents have traditionally been studied using low\u2010throughput, technically challenging approaches, including microneurography in humans and teased fibre electrophysiology in other mammals. Here we suggest a new approach to studying genetically labelled C\u2010LTMRs using <jats:italic>in vivo<\/jats:italic> calcium imaging. We used an automated rotating brush stimulus and von Frey filaments, applied to the hairy skin of anaesthetized mice to mirror light and affective touch. Simultaneously we visualized changes in C\u2010LTMR activity and confirmed that these neurons are sensitive to low\u2010threshold punctate mechanical stimuli and brush stimuli with a strong preference for slow brushing speeds. We also reveal that C\u2010LMTRs are directionally sensitive, showing more activity when brushed against the natural orientation of the hair. We present <jats:italic>in vivo<\/jats:italic> calcium imaging of genetically labelled C\u2010LTMRs as a useful approach that can reveal new aspects of C\u2010LTMR physiology.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16506-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>C\u2010low threshold mechanoreceptors are sensitive to the directionality of a brush stimulus, being preferentially activated by brushing against the grain of the hair, compared with brushing with the grain of the hair. This is surprising as brushing against the grain of the hair is considered less pleasant.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:italic>In vivo<\/jats:italic> calcium imaging is a useful approach to the study of C\u2010low threshold mechanoreceptors.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>While viral transfection, using systemic AAV9, is effective in labelling most sensory neuron populations in the dorsal root ganglion, it fails to label C\u2010low threshold mechanoreceptors.\n<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp286631","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T09:08:16Z","timestamp":1736932096000},"page":"895-908","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<i>In vivo<\/i> calcium imaging reveals directional sensitivity of C\u2010low threshold mechanoreceptors"],"prefix":"10.1113","volume":"603","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9753-6124","authenticated-orcid":false,"given":"Evangelia","family":"Semizoglou","sequence":"first","affiliation":[{"name":"Department of Neurology Brigham &amp; Women's Hospital, Harvard Medical School Boston USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laure","family":"Lo Re","sequence":"additional","affiliation":[{"name":"Tafalgie Therapeutics Campus de Luminy Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven J.","family":"Middleton","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences University of Oxford Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4967-5418","authenticated-orcid":false,"given":"Jimena","family":"Perez\u2010Sanchez","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical 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