{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T09:28:30Z","timestamp":1791106110785,"version":"4.1.0"},"reference-count":104,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2007,12,14]],"date-time":"2007-12-14T00:00:00Z","timestamp":1197590400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2007,12,15]]},"abstract":"<jats:p>Huntington's disease (HD) is an autosomal dominant, late onset, neurodegenerative disease characterized by motor deficits and dementia that is caused by expansion of a CAG repeat in the HD gene. Clinical manifestations result from selective neuronal degeneration of predominantly GABAergic striatal medium\u2010sized spiny neurons (MSNs). A growing number of studies demonstrate that personality, mood and cognitive disturbances are some of the earliest signs of HD and may reflect synaptic dysfunction prior to neuronal loss. Previous studies in striatal MSNs demonstrated early alterations in NMDA\u2010type glutamate receptor currents in several HD mouse models, as well as evidence for presynaptic dysfunction prior to disease manifestations in the R6\/2 HD fragment mouse model. We have compared corticostriatal synaptic function in full\u2010length, human HD gene\u2010carrying YAC transgenic mice expressing a non\u2010pathogenic CAG repeat (YAC18; control) with three increasingly severe variants of pathogenic HD gene\u2010expressing mice (YAC72 and two different lines of YAC128), at ages that precede any detectable disease phenotype. We report presynaptic dysfunction and a propensity towards synaptic depression in YAC72 and YAC128 compared to YAC18 mice, and, in the most severe model, we also observed altered AMPA receptor function. When normalized to evoked AMPAR currents, postsynaptic NMDAR currents are augmented in all three pathogenic HD YAC variants. These findings demonstrate multiple perturbations to corticostriatal synaptic function in HD mice, furthering our understanding of the early effects of the HD mutation that may contribute to cognitive dysfunction, mood disorders and later development of more serious dysfunction. Furthermore, this study provides a set of neurophysiological sequelae against which to test and compare other mouse models and potential therapies in HD.<\/jats:p>","DOI":"10.1113\/jphysiol.2007.142448","type":"journal-article","created":{"date-parts":[[2007,10,18]],"date-time":"2007-10-18T20:34:52Z","timestamp":1192739692000},"page":"817-831","source":"Crossref","is-referenced-by-count":117,"title":["Corticostriatal synaptic function in mouse models of Huntington's disease: early effects of huntingtin repeat length and protein load"],"prefix":"10.1113","volume":"585","author":[{"given":"Austen J.","family":"Milnerwood","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn A.","family":"Raymond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,12,14]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.01118.2005"},{"key":"e_1_2_5_3_1","first-page":"1193","article-title":"CAG expansion affects the expression of mutant Huntingtin in the Huntington's disease brain","volume":"15","author":"Aronin N","year":"1995","journal-title":"et al"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0959-4388(92)90035-J"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0447.2002.0o456.x"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/361031a0"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.1244"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-03-00961.2003"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2006.11.001"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.03991.x"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/neu.480230915"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2006.10.016"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl224"},{"key":"e_1_2_5_14_1","volume-title":"Abstract Viewer\/Itinerary Planner, Society for Neuroscience","author":"Dallerac GM","year":"2006"},{"key":"e_1_2_5_15_1","first-page":"1075","article-title":"Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons","volume":"14","author":"DiFiglia M","year":"1995","journal-title":"et al"},{"key":"e_1_2_5_16_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S0031-6997(24)01394-2","article-title":"The glutamate receptor ion channels","volume":"51","author":"Dingledine R","year":"1999","journal-title":"Pharmacol Rev"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11068-004-0514-8"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208171"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.11.034"},{"key":"e_1_2_5_20_1","first-page":"387","article-title":"Trinucleotide repeat length instability and age of onset in Huntington's disease","volume":"4","author":"Duyao M","year":"1993","journal-title":"et al"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4356-06.2007"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2006.11.003"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(03)00065-1"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn832"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(00)00008-7"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2005.08.007"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1831"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00594-4"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0953-816x.2001.01767.x"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0340936"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1570-9639(02)00455-7"},{"key":"e_1_2_5_32_1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group","volume":"72","author":"HDCRG","year":"1993","journal-title":"Cell"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80764-3"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.11.027"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0597-44"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2001.86.6.2667"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3861-04.2005"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2959-05.2005"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05506"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-23-09112.2001"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410370213"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2153"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/123.7.1349"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19991115)58:4<515::AID-JNR5>3.0.CO;2-F"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2004.01.008"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-21-08473.2001"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00308.2004"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg218"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2002.1242"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2005.09.005"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5113-06.2007"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1697-04.2004"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4320-04.2005"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C100401200"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg334"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl092"},{"key":"e_1_2_5_57_1","volume-title":"Abstract Viewer\/Itinerary Planner, Society for Neuroscience","author":"Milnerwood AJ","year":"2006"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-32562-0_32"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.21.2547"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-13-05115.2000"},{"key":"e_1_2_5_61_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2002.1228"},{"key":"e_1_2_5_62_1","doi-asserted-by":"publisher","DOI":"10.1042\/bst0320001"},{"key":"e_1_2_5_63_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.6.883"},{"key":"e_1_2_5_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2005.06.003"},{"key":"e_1_2_5_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(00)00632-9"},{"key":"e_1_2_5_66_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1999.0732441.x"},{"key":"e_1_2_5_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.08.016"},{"key":"e_1_2_5_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(03)00107-7"},{"key":"e_1_2_5_69_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5214-03.2004"},{"key":"e_1_2_5_70_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.068460"},{"key":"e_1_2_5_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.12.056"},{"key":"e_1_2_5_72_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0364-04.2004"},{"key":"e_1_2_5_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2005.08.001"},{"key":"e_1_2_5_74_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.23.2815"},{"key":"e_1_2_5_75_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg169"},{"key":"e_1_2_5_76_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-12-04480.2000"},{"key":"e_1_2_5_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(03)00319-8"},{"key":"e_1_2_5_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropsychologia.2006.12.015"},{"key":"e_1_2_5_79_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20651"},{"key":"e_1_2_5_80_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.013bu.x"},{"key":"e_1_2_5_81_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.26.041002.131412"},{"key":"e_1_2_5_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2007.03.008"},{"key":"e_1_2_5_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.03.040"},{"key":"e_1_2_5_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00569-5"},{"key":"e_1_2_5_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2006.07.030"},{"key":"e_1_2_5_86_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2004.03756.x"},{"key":"e_1_2_5_87_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.18.8195-8209.2004"},{"key":"e_1_2_5_88_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.5.839"},{"key":"e_1_2_5_89_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0590-05.2005"},{"key":"e_1_2_5_90_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1998.79.2.555"},{"key":"e_1_2_5_91_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-198511000-00003"},{"key":"e_1_2_5_92_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2000.00175.x"},{"key":"e_1_2_5_93_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.17.1807"},{"key":"e_1_2_5_94_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.3.487"},{"key":"e_1_2_5_95_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-07-02397.1996"},{"key":"e_1_2_5_96_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2220-05.2005"},{"key":"e_1_2_5_97_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00971.2006"},{"key":"e_1_2_5_98_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4415-06.2007"},{"key":"e_1_2_5_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(94)91320-X"},{"key":"e_1_2_5_100_1","first-page":"276","volume-title":"Huntington's Disease","author":"Yohrling GJ","year":"2002"},{"key":"e_1_2_5_101_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.2000.0909"},{"key":"e_1_2_5_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2003.11.014"},{"key":"e_1_2_5_103_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00615-3"},{"key":"e_1_2_5_104_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1973.sp010167"},{"key":"e_1_2_5_105_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.02.003"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.2007.142448","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.2007.142448","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T14:07:41Z","timestamp":1737468461000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.2007.142448"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,12,14]]},"references-count":104,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2007,12,15]]}},"alternative-id":["10.1113\/jphysiol.2007.142448"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.2007.142448","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1092756.547674","asserted-by":"object"}]},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,12,14]]}}}