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Neurosci."],"published-print":{"date-parts":[[2020,10,7]]},"abstract":"<jats:p>Mammalian taste buds are comprised of specialized neuroepithelial cells that act as sensors for molecules that provide nutrition (e.g., carbohydrates, amino acids, and salts) and those that are potentially harmful (e.g., certain plant compounds and strong acids). Type II and III taste bud cells (TBCs) detect molecules described by humans as \u201csweet,\u201d \u201cbitter,\u201d \u201cumami,\u201d and \u201csour.\u201d TBCs that detect metallic ions, described by humans as \u201csalty,\u201d are undefined. Historically, type I glial-like TBCs have been thought to play a supportive role in the taste bud, but little research has been done to explore their role in taste transduction. Some evidence implies that type I cells may detect sodium (Na<jats:sup>+<\/jats:sup>) via an amiloride-sensitive mechanism, suggesting they play a role in Na<jats:sup>+<\/jats:sup>taste transduction. We used an optogenetic approach to study type I TBCs by driving the expression of the light-sensitive channelrhodopsin-2 (ChR2) in type I GAD65<jats:sup>+<\/jats:sup>TBCs of male and female mice. Optogenetic stimulation of GAD65<jats:sup>+<\/jats:sup>TBCs increased chorda tympani nerve activity and activated gustatory neurons in the rostral nucleus tractus solitarius. \u201cN neurons,\u201d whose NaCl responses were blocked by the amiloride analog benzamil, responded robustly to light stimulation of GAD65<jats:sup>+<\/jats:sup>TBCs on the anterior tongue. Two-bottle preference tests were conducted under Na<jats:sup>+<\/jats:sup>-replete and Na<jats:sup>+<\/jats:sup>-deplete conditions to assess the behavioral impact of optogenetic stimulation of GAD65<jats:sup>+<\/jats:sup>TBCs. Under Na<jats:sup>+<\/jats:sup>-deplete conditions GAD65-ChR2-EYFP mice displayed a robust preference for H<jats:sub>2<\/jats:sub>O illuminated with 470 nm light versus nonilluminated H<jats:sub>2<\/jats:sub>O, suggesting that type I glial-like TBCs are sufficient for driving a behavior that resembles Na<jats:sup>+<\/jats:sup>appetite.<\/jats:p><jats:p><jats:bold>SIGNIFICANCE STATEMENT<\/jats:bold>This is the first investigation on the role of type I GAD65<jats:sup>+<\/jats:sup>taste bud cells (TBCs) in taste-mediated physiology and behavior via optogenetics. It details the first definitive evidence that selective optogenetic stimulation of glial-like GAD65<jats:sup>+<\/jats:sup>TBCs evokes neural activity and modulates behavior. Optogenetic stimulation of GAD65<jats:sup>+<\/jats:sup>TBCs on the anterior tongue had the strongest effect on gustatory neurons that responded best to NaCl stimulation through a benzamil-sensitive mechanism. Na<jats:sup>+<\/jats:sup>-depleted mice showed robust preferences to \u201clight taste\u201d (H<jats:sub>2<\/jats:sub>O illuminated with 470 nm light vs nonilluminated H<jats:sub>2<\/jats:sub>O), suggesting that the activation of GAD65<jats:sup>+<\/jats:sup>cells may generate a salt-taste sensation in the brain. Together, our results shed new light on the role of GAD65<jats:sup>+<\/jats:sup>TBCs in gustatory transduction and taste-mediated behavior.<\/jats:p>","DOI":"10.1523\/jneurosci.0597-20.2020","type":"journal-article","created":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T21:50:17Z","timestamp":1599083417000},"page":"7795-7810","source":"Crossref","is-referenced-by-count":27,"title":["Optogenetic Stimulation of Type I GAD65<sup>+<\/sup>Cells in Taste Buds Activates Gustatory Neurons and Drives Appetitive Licking Behavior in Sodium-Depleted Mice"],"prefix":"10.1523","volume":"40","author":[{"given":"Caitlin","family":"Baumer-Harrison","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5202-814X","authenticated-orcid":false,"given":"Martin A.","family":"Raymond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Myers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kolbe M.","family":"Sussman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spencer T.","family":"Rynberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda P.","family":"Ugartechea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean","family":"Lauterbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Mast","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Breza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2020,9,2]]},"reference":[{"key":"2023041803432779000_40.41.7795.1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20954"},{"key":"2023041803432779000_40.41.7795.2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"2023041803432779000_40.41.7795.3","doi-asserted-by":"publisher","DOI":"10.1093\/chemse\/bjx013"},{"key":"2023041803432779000_40.41.7795.4","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00843.2009"},{"key":"2023041803432779000_40.41.7795.5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0146475"},{"key":"2023041803432779000_40.41.7795.6","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1993.264.2.R319"},{"key":"2023041803432779000_40.41.7795.7","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00114.2012"},{"key":"2023041803432779000_40.41.7795.8","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00621.2011"},{"key":"2023041803432779000_40.41.7795.9","doi-asserted-by":"publisher","DOI":"10.1093\/chemse\/bjw055"},{"key":"2023041803432779000_40.41.7795.10","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00793.2005"},{"key":"2023041803432779000_40.41.7795.11","doi-asserted-by":"publisher","DOI":"10.1093\/chemse\/bjm052"},{"key":"2023041803432779000_40.41.7795.12","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00785.2009"},{"key":"2023041803432779000_40.41.7795.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2004.03.009"},{"key":"2023041803432779000_40.41.7795.14","doi-asserted-by":"publisher","DOI":"10.1038\/nature08783"},{"key":"2023041803432779000_40.41.7795.15","unstructured":"Cohen J (1988) Statistical power analysis for the behavioral sciences, Ed 2. 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