{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:09:44Z","timestamp":1791306584778,"version":"4.3.1"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T00:00:00Z","timestamp":1436832000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2862"],"award-info":[{"award-number":["2862"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["3050"],"award-info":[{"award-number":["3050"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003945","name":"Link\u00f6pings Universitet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003945","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Brain and Behavior"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:p>Behavioral flexibility is a complex cognitive function that is necessary for survival in changeable environments. Patients with schizophrenia or Parkinson's disease often suffer from cognitive rigidity, reducing their capacity to function in society. Patients and rodent models with focal lesions in the prefrontal cortex (<jats:styled-content style=\"fixed-case\">PFC<\/jats:styled-content>) show similar rigidity, owing to the loss of <jats:styled-content style=\"fixed-case\">PFC<\/jats:styled-content> regulation of subcortical reward circuits involved in behavioral flexibility. The vesicular glutamate transporter (<jats:styled-content style=\"fixed-case\">VGluT1<\/jats:styled-content>) is preferentially expressed at modulatory synapses, including <jats:styled-content style=\"fixed-case\">PFC<\/jats:styled-content> neurons that project to components of the reward circuit (such as the nucleus accumbens, NAc). <jats:styled-content style=\"fixed-case\">VGluT1<\/jats:styled-content><jats:sup>+\/\u2212<\/jats:sup> mice display behavioral phenotypes matching many symptoms of schizophrenia, and <jats:styled-content style=\"fixed-case\">VGluT1<\/jats:styled-content> expression is reduced in the <jats:styled-content style=\"fixed-case\">PFC<\/jats:styled-content> of patients with schizophrenia and Parkinson's disease. Thus, it appears likely that <jats:styled-content style=\"fixed-case\">VGluT1<\/jats:styled-content>\u2010expressing synapses from <jats:styled-content style=\"fixed-case\">PFC<\/jats:styled-content> play a key role in behavioral flexibility. To examine this hypothesis, we studied behavioral flexibility in <jats:styled-content style=\"fixed-case\">VGluT1<\/jats:styled-content><jats:sup>+\/\u2212<\/jats:sup> mice by testing reversal learning in a visual discrimination task. Here, we show that <jats:styled-content style=\"fixed-case\">VGluT1<\/jats:styled-content><jats:sup>+\/\u2212<\/jats:sup> mice acquired the initial visual discrimination at the same rate as controls. However, they failed to suppress responses to the previously rewarded stimulus following reversal of reward contingencies. Thus, our genetic disruption of modulatory glutamatergic signaling, including that arising from <jats:styled-content style=\"fixed-case\">PFC<\/jats:styled-content>, appears to have impaired the first stage of reversal learning (extinguishing responses to previously rewarded stimuli). Our data show that this deficit stems from a preservative phenotype. These findings suggest that glutamatergic regulation from the cortex is important for behavioral flexibility and the disruption of this pathway may be relevant in diseases such as schizophrenia.<\/jats:p>","DOI":"10.1111\/gbb.12230","type":"journal-article","created":{"date-parts":[[2015,6,26]],"date-time":"2015-06-26T05:40:59Z","timestamp":1435297259000},"page":"477-485","source":"Crossref","is-referenced-by-count":23,"title":["The initial stage of reversal learning is impaired in mice hemizygous for the vesicular glutamate transporter (<scp>VGluT1<\/scp>)"],"prefix":"10.1111","volume":"14","author":[{"given":"B.","family":"Granseth","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Division of Cell Biology Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. 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H.","family":"Lindstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Division of Cell Biology Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,14]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/124.8.1492"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchemneu.2013.02.007"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhp133"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21265"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchemneu.2007.08.001"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2013.01.042"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2010.02.017"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-25-08771.2003"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0953-816x.2001.01607.x"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-2626(03)00284-7"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2007.10.005"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2004.05.010"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2008.12.001"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.012959"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1097468"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10848"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2004.03807.x"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0012-07.2007"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1471"},{"key":"e_1_2_5_21_1","volume-title":"Neuroscience 2014 Abstracts","author":"Granseth B.","year":"2014"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/gbb.12191"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2013.122"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2011.12.012"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1076\/chin.8.2.93.8726"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2006.02.010"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2014.05.032"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2007.05868.x"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.07.033"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1401.013"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2815-12.2012"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2012.00195"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2006.05259.x"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5851-08.2009"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2007.03.010"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1420-9101.2005.00917.x"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401764101"}],"container-title":["Genes, Brain and Behavior"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fgbb.12230","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/gbb.12230","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T07:10:13Z","timestamp":1696317013000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/gbb.12230"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7]]},"references-count":36,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,7]]}},"alternative-id":["10.1111\/gbb.12230"],"URL":"https:\/\/doi.org\/10.1111\/gbb.12230","archive":["Portico"],"relation":{},"ISSN":["1601-1848","1601-183X"],"issn-type":[{"value":"1601-1848","type":"print"},{"value":"1601-183X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7]]}}}