{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T22:49:14Z","timestamp":1773010154273,"version":"3.50.1"},"posted":{"date-parts":[[2024,9,19]]},"group-title":"Neuroscience","reference-count":44,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T00:00:00Z","timestamp":1726704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,9,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Engagement of the striatum (caudate\/putamen) and other basal ganglia nuclei during seizures was first observed over 75 years ago. Basal ganglia output nuclei, and the substantia nigra pars reticulata, in particular, have well-established anti-seizure effects across a large array of experimental models. However, striatal control of seizures is understudied. To address this gap, we used optogenetic approaches to activate and inactivate neurons in the dorsal striatum of Sprague-Dawley rats submitted to the gamma-butyrolactone (GBL) model of absence epilepsy, amygdala kindling model of temporal lobe epilepsy, and pilocarpine-induced Status Epilepticus (SE). All tests were performed on a within-subject basis. Animals were tested in two different light frequencies (5 Hz and 100 Hz). Open-loop (continuous light delivery) optogenetic activation of the dorsal striatal neurons robustly suppressed seizures in all models. On the other hand, optogenetic silencing of the dorsal striatal neurons increased absence seizure expression and facilitated SE onset but had no effect on kindled limbic seizures. In the GBL model, we also verified if the closed- loop strategy (light delivery in response to seizure detection) would be enough to induce antiseizure effects. On-demand light delivery in ChR2-expressing animals reduced SWD duration, while the same approach in ArchT-expressing animals increased SWD duration. These results demonstrated previously unrecognized anti-absence effects associated with striatal continuous and on-demand neuromodulation. Together, these findings document a robust, bidirectional role of the dorsal striatum in the control of seizure generation and propagation in a variety of seizure models, including focal seizure onset and generalized seizures.<\/jats:p>","DOI":"10.1101\/2024.09.18.613710","type":"posted-content","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T07:11:10Z","timestamp":1726729870000},"source":"Crossref","is-referenced-by-count":2,"title":["Optogenetic stimulation of dorsal striatum bidirectionally controls seizures"],"prefix":"10.64898","author":[{"given":"Safwan K.","family":"Hyder","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Willian","family":"Lazarini-Lopes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Toib","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabrielle","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Sukharev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick A.","family":"Forcelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024092308300662000_2024.09.18.613710v1.1","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1152\/jn.1951.14.4.305","article-title":"Electrophysiological studies of subcortical connections of anterior temporal region in cat","volume":"14","year":"1951","journal-title":"J. Neurophysiol"},{"key":"2024092308300662000_2024.09.18.613710v1.2","doi-asserted-by":"crossref","unstructured":"G. B. Udvarhelyi , Dissemination of Acute Focal Seizures In the Monkey: I. From Cortical Foci. Arch. Neurol. 12, 333 (1965).","DOI":"10.1001\/archneur.1965.00460280003001"},{"key":"2024092308300662000_2024.09.18.613710v1.3","doi-asserted-by":"publisher","DOI":"10.1126\/science.7146907"},{"key":"2024092308300662000_2024.09.18.613710v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(87)90289-5"},{"key":"2024092308300662000_2024.09.18.613710v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(89)91434-0"},{"key":"2024092308300662000_2024.09.18.613710v1.6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1528-1157.1987.tb03613.x","article-title":"The Substantia Nigra is an Important Site for the Containment of Seizure Generalization in the Kindling Model of Epilepsy","volume":"28","year":"1987","journal-title":"Epilepsia"},{"key":"2024092308300662000_2024.09.18.613710v1.7","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1908176117"},{"key":"2024092308300662000_2024.09.18.613710v1.8","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad166"},{"key":"2024092308300662000_2024.09.18.613710v1.9","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.nbd.2015.12.012","article-title":"Optogenetic activation of superior colliculus neurons suppresses seizures originating in diverse brain networks","volume":"87","year":"2016","journal-title":"Neurobiol. Dis"},{"key":"2024092308300662000_2024.09.18.613710v1.10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.5.1694"},{"key":"2024092308300662000_2024.09.18.613710v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(86)91204-7"},{"key":"2024092308300662000_2024.09.18.613710v1.12","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1093\/brain\/awab119","article-title":"Activation of the basal ganglia and indirect pathway neurons during frontal lobe seizures","volume":"144","year":"2021","journal-title":"Brain"},{"key":"2024092308300662000_2024.09.18.613710v1.13","doi-asserted-by":"crossref","unstructured":"D. F. Aschauer , S. Kreuz , S. Rumpel , Analysis of Transduction Efficiency, Tropism and Axonal Transport of AAV Serotypes 1, 2, 5, 6, 8 and 9 in the Mouse Brain. PLoS ONE 8, e76310 (2013).","DOI":"10.1371\/journal.pone.0076310"},{"key":"2024092308300662000_2024.09.18.613710v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2376"},{"key":"2024092308300662000_2024.09.18.613710v1.15","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac051"},{"key":"2024092308300662000_2024.09.18.613710v1.16","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab042"},{"key":"2024092308300662000_2024.09.18.613710v1.17","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa450"},{"key":"2024092308300662000_2024.09.18.613710v1.18","doi-asserted-by":"crossref","unstructured":"E. Krook-Magnuson , G. G. Szabo , C. Armstrong , M. Oijala , I. Soltesz , Cerebellar Directed Optogenetic Intervention Inhibits Spontaneous Hippocampal Seizures in a Mouse Model of Temporal Lobe Epilepsy. eNeuro 1 (2014).","DOI":"10.1523\/ENEURO.0005-14.2014"},{"key":"2024092308300662000_2024.09.18.613710v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2016.07.003"},{"key":"2024092308300662000_2024.09.18.613710v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/0013-4694(72)90177-0"},{"key":"2024092308300662000_2024.09.18.613710v1.21","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.08-11-04027.1988"},{"key":"2024092308300662000_2024.09.18.613710v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(98)00053-9"},{"key":"2024092308300662000_2024.09.18.613710v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2020.10.016"},{"key":"2024092308300662000_2024.09.18.613710v1.24","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19990816)411:1<145::AID-CNE11>3.0.CO;2-1"},{"key":"2024092308300662000_2024.09.18.613710v1.25","first-page":"S9","article-title":"Functional organization of the circuits connecting the cerebral cortex and the basal ganglia: implications for the role of the basal ganglia in epilepsy","volume":"4","year":"2002","journal-title":"Epileptic. Disord"},{"key":"2024092308300662000_2024.09.18.613710v1.26","doi-asserted-by":"crossref","unstructured":"S. Br\u00f6er , Not Part of the Temporal Lobe, but Still of Importance? Substantia Nigra and Subthalamic Nucleus in Epilepsy. Front. Syst. Neurosci. 14 (2020).","DOI":"10.3389\/fnsys.2020.581826"},{"key":"2024092308300662000_2024.09.18.613710v1.27","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4932-12.2013"},{"key":"2024092308300662000_2024.09.18.613710v1.28","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/0006-8993(81)90195-5","article-title":"Effect of stimulation of the putamen on the substantia nigra in the cat","volume":"217","year":"1981","journal-title":"Brain Res"},{"key":"2024092308300662000_2024.09.18.613710v1.29","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1528-04.2004"},{"key":"2024092308300662000_2024.09.18.613710v1.30","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19960318)366:4<580::AID-CNE3>3.0.CO;2-0"},{"key":"2024092308300662000_2024.09.18.613710v1.31","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00678.2019"},{"key":"2024092308300662000_2024.09.18.613710v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(00)00266-9"},{"key":"2024092308300662000_2024.09.18.613710v1.33","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10165"},{"key":"2024092308300662000_2024.09.18.613710v1.34","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.2000.19640501.x"},{"key":"2024092308300662000_2024.09.18.613710v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(82)90202-0"},{"key":"2024092308300662000_2024.09.18.613710v1.36","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(83)90151-X"},{"key":"2024092308300662000_2024.09.18.613710v1.37","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20741"},{"key":"2024092308300662000_2024.09.18.613710v1.38","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-27577-w"},{"key":"2024092308300662000_2024.09.18.613710v1.39","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1002\/mds.25215","article-title":"Topography of dyskinesias and torticollis evoked by inhibition of substantia nigra pars reticulata","volume":"28","year":"2013","journal-title":"Mov. Disord. Off. J. Mov. Disord. Soc"},{"key":"2024092308300662000_2024.09.18.613710v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2015.06.010"},{"key":"2024092308300662000_2024.09.18.613710v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2018.09.007"},{"key":"2024092308300662000_2024.09.18.613710v1.42","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1998.6928"},{"key":"2024092308300662000_2024.09.18.613710v1.43","doi-asserted-by":"publisher","DOI":"10.1016\/0920-1211(95)00025-6"},{"key":"2024092308300662000_2024.09.18.613710v1.44","unstructured":"G. Paxinos , C. Watson , The Rat Brain in Stereotaxic Coordinates: Hard Cover Edition (Elsevier, 2006)."}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.09.18.613710","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T07:04:48Z","timestamp":1768460688000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.09.18.613710"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,19]]},"references-count":44,"URL":"https:\/\/doi.org\/10.1101\/2024.09.18.613710","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1073\/pnas.2419178122","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2024,9,19]]},"subtype":"preprint"}}