{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:48:39Z","timestamp":1791330519105,"version":"4.3.1"},"reference-count":73,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,5,27]],"date-time":"2015-05-27T00:00:00Z","timestamp":1432684800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"Netherlands Organisation for Health Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Disrupting thalamocortical activity patterns has proven to be a promising approach to stop generalized spike\u2010and\u2010wave discharges (GSWDs) characteristic of absence seizures. Here, we investigated to what extent modulation of neuronal firing in cerebellar nuclei (CN), which are anatomically in an advantageous position to disrupt cortical oscillations through their innervation of a wide variety of thalamic nuclei, is effective in controlling absence seizures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Two unrelated mouse models of generalized absence seizures were used: the natural mutant\n                      <jats:italic>tottering<\/jats:italic>\n                      , which is characterized by a missense mutation in\n                      <jats:italic>Cacna1a<\/jats:italic>\n                      , and inbred\n                      <jats:italic>C3H\/HeOuJ<\/jats:italic>\n                      . While simultaneously recording single CN neuron activity and electrocorticogram in awake animals, we investigated to what extent pharmacologically increased or decreased CN neuron activity could modulate GSWD occurrence as well as short\u2010lasting, on\u2010demand CN stimulation could disrupt epileptic seizures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that a subset of CN neurons show phase\u2010locked oscillatory firing during GSWDs and that manipulating this activity modulates GSWD occurrence. Inhibiting CN neuron action potential firing by local application of the \u03b3\u2010aminobutyric acid type A (GABA\u2010A) agonist muscimol increased GSWD occurrence up to 37\u2010fold, whereas increasing the frequency and regularity of CN neuron firing with the use of GABA\u2010A antagonist gabazine decimated its occurrence. A single short\u2010lasting (30\u2013300 milliseconds) optogenetic stimulation of CN neuron activity abruptly stopped GSWDs, even when applied unilaterally. Using a closed\u2010loop system, GSWDs were detected and stopped within 500 milliseconds.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>CN neurons are potent modulators of pathological oscillations in thalamocortical network activity during absence seizures, and their potential therapeutic benefit for controlling other types of generalized epilepsies should be evaluated. Ann Neurol 2015;77:1027\u20131049<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.24399","type":"journal-article","created":{"date-parts":[[2015,3,11]],"date-time":"2015-03-11T19:37:31Z","timestamp":1426102651000},"page":"1027-1049","source":"Crossref","is-referenced-by-count":143,"title":["Cerebellar output controls generalized spike\u2010and\u2010wave discharge occurrence"],"prefix":"10.1002","volume":"77","author":[{"given":"Lieke","family":"Kros","sequence":"first","affiliation":[{"name":"Department of Neuroscience Erasmus Medical Center Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar H. 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