{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T17:43:49Z","timestamp":1789062229871,"version":"build-2803163510"},"reference-count":76,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T00:00:00Z","timestamp":1645488000000},"content-version":"am","delay-in-days":343,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T00:00:00Z","timestamp":1615852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21MH105846"],"award-info":[{"award-number":["R21MH105846"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005310","name":"Klarman Family Foundation","doi-asserted-by":"publisher","award":["P30 EY13079"],"award-info":[{"award-number":["P30 EY13079"]}],"id":[{"id":"10.13039\/100005310","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Synapse"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Severe voluntary food restriction is the defining symptom of anorexia nervosa (AN), but anxiety and excessive exercise are maladaptive symptoms that contribute significantly to the severity of AN and which individuals with AN have difficulty suppressing. We hypothesized that the excitability of hippocampal pyramidal neurons, known to contribute to anxiety, leads to the maladaptive behavior of excessive exercise. Conversely, since glutamate transporter GLT\u20101 dampens the excitability of hippocampal pyramidal neurons through the uptake of ambient glutamate and suppression of the GluN2B\u2010subunit containing NMDA receptors (GluN2B\u2010NMDARs), GLT\u20101 may contribute toward dampening excessive exercise. This hypothesis was tested using the mouse model of AN, called activity\u2010based anorexia (ABA), whereby food restriction evokes the maladaptive behavior of excessive wheel running (food restriction\u2010evoked running, FRER). We tested whether individual differences in ABA vulnerability of mice, quantified based on FRER, correlated with individual differences in the levels of GLT\u20101 at excitatory synapses of the hippocampus. Electron microscopic immunocytochemistry (EM\u2010ICC) was used to quantify GLT\u20101 levels at the excitatory synapses of the hippocampus. The FRER seen in individual mice varied more than 10\u2010fold, and Pearson correlation analyses revealed a strong negative correlation (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.02) between FRER and GLT\u20101 levels at the axon terminals of excitatory synapses and at the surrounding astrocytic plasma membranes. Moreover, synaptic levels of GluN2B\u2010NMDARs correlated strongly with GLT\u20101 levels at perisynaptic astrocytic plasma membranes. There is at present no accepted pharmacotherapy for AN, and little is known about the etiology of this deadly illness. Current findings suggest that drugs increasing GLT\u20101 expression may reduce AN severity through the reduction of GluN2B\u2010NMDAR activity.<\/jats:p>","DOI":"10.1002\/syn.22197","type":"journal-article","created":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T07:58:57Z","timestamp":1614067137000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Suppression of food restriction\u2010evoked hyperactivity in activity\u2010based anorexia animal model through glutamate transporters GLT\u20101 at excitatory synapses in the hippocampus"],"prefix":"10.1002","volume":"75","author":[{"given":"Olesia M.","family":"Bilash","sequence":"first","affiliation":[{"name":"The Neuroscience Institute NYU Langone Medical Center New York NY USA"},{"name":"Center for Neural Science New York University New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah S.","family":"Actor\u2010Engel","sequence":"additional","affiliation":[{"name":"Center for Neural Science New York University New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang D.","family":"Sherpa","sequence":"additional","affiliation":[{"name":"Center for Neural Science New York University New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Neural Science New York University New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4010-9425","authenticated-orcid":false,"given":"Chiye","family":"Aoki","sequence":"additional","affiliation":[{"name":"The Neuroscience Institute NYU Langone Medical Center New York NY USA"},{"name":"Center for Neural Science New York University New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.141215898"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2016.01.019"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(02)03962-8"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22137"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22151"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.21528"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2014.01.011"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2011.74"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1655-19.2020"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pscychresns.2014.10.013"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2007.02703.x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-108X(199401)15:1<21::AID-EAT2260150104>3.0.CO;2-K"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/eat.20164"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2011.04.023"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-008-1102-2"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1586-03.2004"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2018.04.008"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-016-1341-7"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.22034"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhv087"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-013-0612-9"},{"key":"e_1_2_8_23_1","first-page":"e52927","article-title":"Using the activity\u2010based anorexia rodent model to study the neurobiological basis of anorexia nervosa","volume":"104","author":"Chowdhury T.","year":"2015","journal-title":"Journal of Visualized Experiments"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.22320"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhy283"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2013.03.020"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(02)00028-3"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(00)00067-8"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2016.05.009"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005053-199906000-00002"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brat.2009.09.009"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1825-17.2017"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.11.031"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(03)00341-5"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1179\/1476830515Y.0000000020"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2013.09.073"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-008-8029-y"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/eat.22095"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19981115)54:4<444::AID-JNR2>3.0.CO;2-3"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-9384(03)00102-1"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2020.109921"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(86)90513-7"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1037\/a0015896"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(91)90009-Z"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.161.12.2215"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2009.07.018"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/0010-440X(78)90072-X"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/0376-6357(85)90102-0"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1042\/bst0310865"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.2460\/ajvr.2000.61.969"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2014.0210"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.03581"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1159\/000362328"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.2165\/00007256-200029030-00003"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4255-14.2015"},{"key":"e_1_2_8_56_1","volume-title":"The fine structure of the nervous system: Neurons and their supporting cells","author":"Peters A.","year":"1991"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1177\/43.3.7532656"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0704391104"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80086-0"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03180"},{"key":"e_1_2_8_61_1","article-title":"Food restriction engages prefrontal corticostriatal cells and local microcircuitry to drive the decision to run versus conserve energy","author":"Santiago A. N.","journal-title":"Cerebral Cortex"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(90)90079-J"},{"key":"e_1_2_8_63_1","volume-title":"Clinician's handbook of preventive services: Put prevention into practice","author":"Services, U. D. o. H. a. H","year":"1998"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.11147"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1868"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1184245"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2006.06.020"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/da.20411"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.152.7.1073"},{"key":"e_1_2_8_70_1","first-page":"621","article-title":"The Neurochemical profiles of the dorsal hippocampus and the antiaversive effects of anxiolytics in different models of anxiety in rats","volume":"43","author":"Talaenko A. N.","year":"1993","journal-title":"The Journal of Nervous and Mental Disease"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.janxdis.2011.03.010"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903480304"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-16-06897.1999"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.21690"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1037\/bne0000040"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0439-2"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1002\/eat.20862"}],"container-title":["Synapse"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/syn.22197","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/syn.22197","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/am-pdf\/10.1002\/syn.22197","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/syn.22197","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T04:37:51Z","timestamp":1693629471000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/syn.22197"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,16]]},"references-count":76,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1002\/syn.22197"],"URL":"https:\/\/doi.org\/10.1002\/syn.22197","archive":["Portico"],"relation":{},"ISSN":["0887-4476","1098-2396"],"issn-type":[{"value":"0887-4476","type":"print"},{"value":"1098-2396","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,16]]},"assertion":[{"value":"2021-01-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e22197"}}