{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:48:09Z","timestamp":1787017689061,"version":"build-2736575974"},"reference-count":51,"publisher":"American Physiological Society","issue":"6","funder":[{"DOI":"10.13039\/100006500","name":"Cure Huntington's Disease Initiative","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006500","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["T32 NS058280"],"award-info":[{"award-number":["T32 NS058280"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[2019,12,1]]},"abstract":"<jats:p>Abnormal communication between cerebral cortex and striatum plays a major role in the motor symptoms of Huntington\u2019s disease (HD), a neurodegenerative disorder caused by a mutation of the huntingtin gene ( mHTT). Because cortex is the main driver of striatal processing, we recorded local field potential (LFP) activity simultaneously in primary motor cortex (M1) and dorsal striatum (DS) in BACHD mice, a full-length HD gene model, and in a conditional BACHD\/Emx-1 Cre (BE) model in which mHTT is suppressed in cortical efferents, while mice freely explored a plus-shaped maze beginning at 20 wk of age. Relative to wild-type (WT) controls, BACHD mice were just as active across &gt;40 wk of testing but became progressively less likely to turn into a perpendicular arm as they approached the choice point of the maze, a sign of HD motor inflexibility. BE mice, in contrast, turned as freely as WT throughout testing. Although BE mice did not exactly match WT in LFP activity, the reduction in alpha (8\u201313 Hz), beta (13\u201330 Hz), and low-gamma (30\u201350 Hz) power that occurred in M1 of turning-impaired BACHD mice was reversed. No reversal occurred in DS. In fact, BE mice showed further reductions in DS theta (4\u20138 Hz), beta, and low-gamma power relative to the BACHD model. Coherence analysis indicated a dysregulation of corticostriatal information flow in both BACHD and BE mice. Collectively, our results suggest that mHTT in cortical outputs drives the dysregulation of select cortical frequencies that accompany the loss of behavioral flexibility in HD.<\/jats:p>\n                  <jats:p>NEW &amp; NOTEWORTHY BACHD mice, a full-length genetic model of Huntington\u2019s disease (HD), express aberrant local field potential (LFP) activity in primary motor cortex (M1) along with decreased probability of turning into a perpendicular arm of a plus-shaped maze, a motor inflexibility phenotype. Suppression of the mutant huntingtin gene in cortical output neurons prevents decline in turning and improves alpha, beta, and low-gamma activity in M1. Our results implicate cortical networks in the search for therapeutic strategies to alleviate HD motor signs.<\/jats:p>","DOI":"10.1152\/jn.00777.2018","type":"journal-article","created":{"date-parts":[[2019,11,6]],"date-time":"2019-11-06T14:40:28Z","timestamp":1573051228000},"page":"2621-2629","source":"Crossref","is-referenced-by-count":7,"title":["Lack of mutant huntingtin in cortical efferents improves behavioral inflexibility and corticostriatal dynamics in Huntington\u2019s disease mice"],"prefix":"10.1152","volume":"122","author":[{"given":"Ana Mar\u00eda","family":"Estrada-S\u00e1nchez","sequence":"first","affiliation":[{"name":"Program in Neuroscience and Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana"},{"name":"Departmento de Biolog\u00eda Molecular, Instituto Potosino De Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica, San Luis Potos\u00ed, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney 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