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Genome-wide association studies (GWAS) have identified mutations in\n                    <jats:italic>BTBD9<\/jats:italic>\n                    conferring a higher risk of RLS. Knockout of the\n                    <jats:italic>BTBD9<\/jats:italic>\n                    homolog in mice (\n                    <jats:italic>Btbd9<\/jats:italic>\n                    ) and fly results in motor restlessness and sleep disruption. Clinical studies have found RLS patients have structural and functional abnormalities in the striatum; however, whether and how striatal pathology contributes to the pathogenesis of RLS is not known. Here, we used fMRI to map regions of altered synaptic activity in basal ganglia of systematic\n                    <jats:italic>Btbd9<\/jats:italic>\n                    knock-out (KO) mice. We further dissected striatal circuits using patch-clamp electrophysiological recordings in brain slices. Two different mouse models were generated to test the effect of specific knockout of\n                    <jats:italic>Btbd9<\/jats:italic>\n                    in either striatal medium spiny neurons (MSNs) or cholinergic interneurons (ChIs) using the electrophysiological recording, motor and sensory behavioral tests. We found that\n                    <jats:italic>Btbd9<\/jats:italic>\n                    KO mice showed enhanced neural activity in the striatum, increased postsynaptic currents in the MSNs, and decreased excitability of the striatal ChIs. Knocking out\n                    <jats:italic>Btbd9<\/jats:italic>\n                    specifically in the striatal MSNs, but not the ChIs, led to rest-phase specific motor restlessness, sleep disturbance, and increased thermal sensation in mice, which are consistent with results obtained from the\n                    <jats:italic>Btbd9<\/jats:italic>\n                    KO mice. Our data establish the role of\n                    <jats:italic>Btbd9<\/jats:italic>\n                    in regulating the activity of striatal neurons. Increased activity of the striatal MSNs, possibly through modulation by the striatal ChIs, contributes to the pathogenesis of RLS.\n                  <\/jats:p>","DOI":"10.1523\/eneuro.0277-19.2019","type":"journal-article","created":{"date-parts":[[2019,8,23]],"date-time":"2019-08-23T17:45:33Z","timestamp":1566582333000},"page":"ENEURO.0277-19.2019","source":"Crossref","is-referenced-by-count":31,"title":["The Role of BTBD9 in Striatum and Restless Legs Syndrome"],"prefix":"10.1523","volume":"6","author":[{"given":"Shangru","family":"Lyu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark 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