{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T23:13:05Z","timestamp":1787353985638,"version":"build-2736575974"},"reference-count":71,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,3,25]],"date-time":"2018-03-25T00:00:00Z","timestamp":1521936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21NS086117"],"award-info":[{"award-number":["R21NS086117"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Comparative Neurology"],"published-print":{"date-parts":[[2018,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Somatosensation is a complex sense mediated by more than a dozen distinct neural subtypes in the periphery. Although pressure and touch sensation have been mapped to primary somatosensory cortex in rodents, it has been controversial whether pain and temperature inputs are also directed to this area. Here we use a well\u2010defined somatosensory modality, cool sensation mediated by peripheral TrpM8\u2010receptors, to investigate the neural substrate for cool perception in the mouse neocortex. Using activation of cutaneous TrpM8 receptor\u2010expressing neurons, we identify candidate neocortical areas responsive for cool sensation. Initially, we optimized TrpM8 stimulation and determined that menthol, a selective TrpM8 agonist, was more effective than cool stimulation at inducing expression of the immediate\u2010early gene <jats:italic>c\u2010fos<\/jats:italic> in the spinal cord. We developed a broad\u2010scale brain survey method for identification of activated brain areas, using automated methods to quantify c\u2010fos immunoreactivity (fos\u2010IR) across animals. Brain areas corresponding to the posterior insular cortex and secondary somatosensory (S2) show elevated fos\u2010IR after menthol stimulation, in contrast to weaker activation in primary somatosensory cortex (S1). In addition, menthol exposure triggered fos\u2010IR in piriform cortex, the amygdala, and the hypothalamus. Menthol\u2010mediated activation was absent in TrpM8\u2010knock\u2010out animals. Our results indicate that cool somatosensory input broadly drives neural activity across the mouse brain, with neocortical signal most elevated in the posterior insula, as well as S2 and S1. These findings are consistent with data from humans indicating that the posterior insula is specialized for somatosensory information encoding temperature, pain, and gentle touch.<\/jats:p>","DOI":"10.1002\/cne.24418","type":"journal-article","created":{"date-parts":[[2018,2,27]],"date-time":"2018-02-27T01:12:44Z","timestamp":1519693964000},"page":"1444-1456","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["TrpM8\u2010mediated somatosensation in mouse neocortex"],"prefix":"10.1002","volume":"526","author":[{"given":"Patrick","family":"Beukema","sequence":"first","affiliation":[{"name":"Department of Neuroscience Center for Neuroscience at the University of Pittsburgh Pittsburgh Pennsylvania 15260"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine L.","family":"Cecil","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine Houston Texas 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Peterson","sequence":"additional","affiliation":[{"name":"Department of Psychology University of California Los Angeles Los Angeles, CA 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor R.","family":"Mann","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of California Berkeley California 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumi","family":"Matsushita","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Center for the Neural Basis of Cognition Carnegie Mellon University Pittsburgh Pennsylvania 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Takashima","sequence":"additional","affiliation":[{"name":"Department of Psychology University of California Los Angeles Los Angeles, CA 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saket","family":"Navlakha","sequence":"additional","affiliation":[{"name":"Integrative Biology Laboratory The Salk Institute for Biological Studies La Jolla California 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7092-1356","authenticated-orcid":false,"given":"Alison L.","family":"Barth","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Center for the Neural Basis of Cognition Carnegie Mellon University Pittsburgh Pennsylvania 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1532-2149.2014.501.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4737-03.2004"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00253.2010"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05910"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2010.08.056"},{"key":"e_1_2_7_7_1","first-page":"231","article-title":"The conduction of pain above the level of the thalamus opticus","author":"Biemond A.","year":"1955","journal-title":"AMA Archives of Neurology and Psychiatry"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2004.05.021"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000181351.82772.b3"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2005.03.041"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1975.38.1.1"},{"key":"e_1_2_7_12_1","doi-asserted-by":"crossref","unstructured":"Brunelli R.(2009). Template Matching Techniques in Computer Vision: Theory and Practice: John Wiley & Sons.","DOI":"10.1002\/9780470744055"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.14.7705"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1996.76.1.571"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.04.017"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.26.041002.131022"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2555"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2606-c1"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/72131"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1998.80.3.1533"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00084.2004"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.02.024"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.21416"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409753102"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2012.03.012"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2003.07.004"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-19-07252.1997"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awg032"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3272-03.2004"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(99)00021-4"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.90564.2008"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(92)90109-O"},{"key":"e_1_2_7_33_1","volume-title":"Thermal sensations and thermoreceptors in man","author":"Hensel H.","year":"1982"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/50.3-4.413"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.10.035"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511541667"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(03)00101-6"},{"key":"e_1_2_7_38_1","first-page":"57","article-title":"The organization of somatosensory cortex in anthropoid primates","volume":"93","author":"Kaas J. H.","year":"2003","journal-title":"Advances in Neurology"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)02274-X"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2000.84.2.719"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-6622-9_5"},{"key":"e_1_2_7_42_1","volume-title":"Gehirnpathologie","author":"Kleist K.","year":"1934"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(80)90046-1"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903170102"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1957.tb01489.x"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6207-10.2011"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2015.29.4202"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2010.09.003"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3059-12.2012"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.12.072"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature719"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3828"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eurpsy.2007.02.006"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00427.2006"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-53860-4.00007-6"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5128-06.2007"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/12.4.376"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/60.4.389"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.182272899"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1999.81.6.3100"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-999-0043-8"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhn054"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008185"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2994"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3396-14.2014"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-010-0296-3"},{"key":"e_1_2_7_67_1","first-page":"563","article-title":"Der dichte der Kahlpuncte auf der Haut der menschlichen Korper","volume":"91","author":"Strughold H.","year":"1931","journal-title":"Zoologische Biology"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4578-07.2007"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2010.05.039"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(98)00184-5"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.08.069"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.10.027"}],"container-title":["Journal of Comparative Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcne.24418","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cne.24418","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T16:35:28Z","timestamp":1695573328000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cne.24418"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,25]]},"references-count":71,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2018,6,15]]}},"alternative-id":["10.1002\/cne.24418"],"URL":"https:\/\/doi.org\/10.1002\/cne.24418","archive":["Portico"],"relation":{},"ISSN":["0021-9967","1096-9861"],"issn-type":[{"value":"0021-9967","type":"print"},{"value":"1096-9861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,25]]},"assertion":[{"value":"2017-09-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-02-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}