{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T14:54:57Z","timestamp":1781103297060,"version":"3.54.1"},"reference-count":60,"publisher":"National Academy of Sciences","issue":"45","license":[{"start":{"date-parts":[[2015,10,27]],"date-time":"2015-10-27T00:00:00Z","timestamp":1445904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.pnas.org\/site\/misc\/userlicense.xhtml"}],"funder":[{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["U01MH067965"],"award-info":[{"award-number":["U01MH067965"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"HHS | NIH | National Institute of Mental Health","doi-asserted-by":"publisher","award":["5P56-NS071669"],"award-info":[{"award-number":["5P56-NS071669"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"HHS | NIH | National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["ES016931"],"award-info":[{"award-number":["ES016931"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2015,11,10]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Huntington\u2019s disease (HD) is a devastating neurodegenerative genetic disorder characterized by progressive decline of motor control. Although the genetic mutation responsible for the syndrome associated with HD has been clearly identified, a specific treatment for HD is not yet available. Therefore, there is a tremendous need for new therapeutic approaches and new molecular therapeutic targets. Using HD mouse models, we show age-dependent alterations of corticostriatal transmission paralleled by alterations of M\n                    <jats:sub>4<\/jats:sub>\n                    muscarinic acetylcholine receptor (mAChR)-mediated control of corticostriatal glutamate signaling. Also, chronic treatment with the selective M\n                    <jats:sub>4<\/jats:sub>\n                    mAChR positive allosteric modulator VU0467154 improves motor and synaptic deficits in 5-mo-old YAC128 mice. This suggests that M\n                    <jats:sub>4<\/jats:sub>\n                    may represent a therapeutic target for the treatment of HD.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1512812112","type":"journal-article","created":{"date-parts":[[2015,10,28]],"date-time":"2015-10-28T03:31:13Z","timestamp":1446003073000},"page":"14078-14083","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":45,"title":["Allosteric activation of M\n                    <sub>4<\/sub>\n                    muscarinic receptors improve behavioral and physiological alterations in early symptomatic YAC128 mice"],"prefix":"10.1073","volume":"112","author":[{"given":"Tristano","family":"Pancani","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN 37232;"},{"name":"Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Foster","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN 37232;"},{"name":"Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S.","family":"Moehle","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN 37232;"},{"name":"Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry Jo","family":"Bichell","sequence":"additional","affiliation":[{"name":"Department of Neurology, Vanderbilt University, Nashville, TN 37232;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Bradley","sequence":"additional","affiliation":[{"name":"Department of Neurology, Vanderbilt University, Nashville, TN 37232;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Bridges","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN 37232;"},{"name":"Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Klar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN 37232;"},{"name":"Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Poslusney","sequence":"additional","affiliation":[{"name":"Lieber Institute for Brain Development, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerri M.","family":"Rook","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN 37232;"},{"name":"Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Scott","family":"Daniels","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN 37232;"},{"name":"Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen M.","family":"Niswender","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN 37232;"},{"name":"Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie K.","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN 37232;"},{"name":"Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Wood","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN 37232;"},{"name":"Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron B.","family":"Bowman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Vanderbilt University, Nashville, TN 37232;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig W.","family":"Lindsley","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN 37232;"},{"name":"Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixiu","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN 37232;"},{"name":"Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Jeffrey","family":"Conn","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN 37232;"},{"name":"Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2015,10,27]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90585-E"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2010.04.030"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1996.00550060029011"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.69.6.773"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-971176"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2007.128728"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.24"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-03-00961.2003"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11068-004-0514-8"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.01118.2005"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5473-08.2009"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5687-08.2009"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.01.008"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3539-10.2011"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70088-7"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70238-8"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8091209"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.2000.19640519.x"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awf239"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3597-04.2004"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.08-10-03750.1988"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3709-06.2007"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2007.07.008"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2368"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/cn500003z"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/103.1.179"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01704.x"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl252"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2011.08.010"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/cn500128b"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.00804.x"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2009.06501.x"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnsys.2011.00061"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2011.05.005"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.21.2547"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2004.047993"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20651"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2007.12.009"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1806"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1400988111"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2014.09.028"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-1575fje"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1234733"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-07-02744.2003"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2007.03.001"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1632"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh190"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2001.86.6.2667"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3246"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.03.036"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198211253072221"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1992.tb09283.x"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2010.05.005"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10776"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0590-05.2005"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26021"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70245-3"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.18.10483"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1668"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4896-13.2014"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1512812112","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1512812112","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T23:52:53Z","timestamp":1649807573000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1512812112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,27]]},"references-count":60,"journal-issue":{"issue":"45","published-print":{"date-parts":[[2015,11,10]]}},"alternative-id":["10.1073\/pnas.1512812112"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1512812112","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,27]]},"assertion":[{"value":"2015-10-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}