{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:47:08Z","timestamp":1792597628989,"version":"4.5.0"},"reference-count":48,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100005339","name":"American Academy of Neurology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005339","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006309","name":"American Parkinson Disease Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006309","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018128","name":"Ludwig Family Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018128","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In the classical model of basal ganglia circuitry, striatal spiny projection neurons of the direct and indirect pathways (dSPNs, iSPNs) promote and suppress movement, respectively, and exhibit unbalanced activity levels during hypokinetic or hyperkinetic conditions. Most therapies for these conditions are thought to work by rebalancing the relative activity of dSPNs and iSPNs toward normal levels. However, the mechanism of amantadine, which uniquely improves both hypokinetic and hyperkinetic conditions, is poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Our aim was to determine whether amantadine restores motor function by normalizing the balance of dSPN and iSPN activity or through a distinct mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used dual\u2010color two\u2010photon Ca\n                      <jats:sup>2+<\/jats:sup>\n                      imaging in the 6\u2010hydroxydopamine (6\u2010OHDA) mouse model of Parkinson's disease to concurrently monitor dSPN and iSPN dynamics across healthy, hypokinetic (parkinsonian), and hyperkinetic (dyskinetic) conditions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We evaluated both dSPN\/iSPN activity balance and action\u2010specific neural ensemble activity in the dorsolateral striatum. In hypokinetic conditions, levodopa rescued the dSPN\/iSPN imbalance but failed to restore the disrupted activity of the locomotion\u2010specific ensemble. Conversely, amantadine improved locomotion\u2010specific ensemble activity without normalizing the dSPN\/iSPN imbalance. In hyperkinetic conditions, forelimb dyskinesias were characterized by neural activity patterns distinct from those encoding locomotion. Amantadine selectively suppressed the resting activity of forelimb dyskinesia ensembles without affecting locomotion\u2010coding ensembles or restoring pathway balance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Levodopa and amantadine may act through distinct mechanisms, with levodopa normalizing pathway balance and amantadine modulating action\u2010specific neural ensembles. These findings support the importance of action\u2010coding disruptions during hypokinetic and hyperkinetic conditions and suggest that correcting them can restore motor function. \u00a9 2026 International Parkinson and Movement Disorder Society.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.70415","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T06:52:08Z","timestamp":1784789528000},"page":"2723-2736","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Amantadine Modulates Action\u2010Specific Neural Ensembles in Hypokinetic and Hyperkinetic Conditions"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1302-8187","authenticated-orcid":false,"given":"Gaurav","family":"Chattree","sequence":"first","affiliation":[{"name":"Department of Neurology and Neurological Sciences Stanford University  Stanford California USA"},{"name":"CNC Program Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rados\u0142aw","family":"Chrapkiewicz","sequence":"additional","affiliation":[{"name":"CNC Program Stanford University  Stanford California USA"},{"name":"James Clark Center Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Zhang","sequence":"additional","affiliation":[{"name":"CNC Program Stanford University  Stanford California USA"},{"name":"Howard Hughes Medical Institute Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Li","sequence":"additional","affiliation":[{"name":"CNC Program Stanford University  Stanford California USA"},{"name":"James Clark Center Stanford University  Stanford California USA"},{"name":"Department of Biology Stanford University  Stanford California 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