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Loss of cerebellar Purkinje cells (PCs) has been observed in some patients with chronic epilepsy; however, whether PC loss can initiate seizures or exacerbate seizure severity remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We established a mouse model of selective PC ablation in adulthood using the diphtheria toxin (DT)\/DT receptor (DTR) system. Seizure susceptibility (epileptiform discharges, Racine score, and network activation) was assessed thoroughly in two distinct seizure models: the pentylenetetrazol (P\u2010uced acute seizure model and the hippocampal kindling model. Furthermore,\n                      <jats:italic>in vivo<\/jats:italic>\n                      electrophysiology recordings in the deep cerebellar nuclei (DCN) were utilized to explore the single\u2010unit firing characteristics following PC ablation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>One month after intraperitoneal (i.p.) DT injection, PC ablation was successfully induced in adult Pcp2\u2010DTR mice. No spontaneous seizures were observed in mice with PC ablation during 48\u2010h wireless electroencephalography\/electromyography (EEG\/EMG) monitoring. However, PC ablation significantly increased seizure susceptibility in the PTZ\u2010induced acute seizure model and accelerated the kindling process in the hippocampal kindling model. Although baseline DCN firing remained unchanged, these mice displayed a distinct post\u2010ictal DCN electrophysiological signature: significantly enhanced delta\/theta power compared to controls, and a decrease in neuronal firing frequency relative to their own baseline, with firing regularity preserved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Together, these findings suggest that PC ablation contributes to heightened seizure susceptibility and seizure severity, highlighting a modulatory role of cerebellar circuits in epilepsy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70177","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T16:01:03Z","timestamp":1773763263000},"page":"3122-3140","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ablation of cerebellar Purkinje cells enhances seizure susceptibility and promotes kindling"],"prefix":"10.1002","volume":"67","author":[{"given":"Kexian","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology Zhongshan Hospital, Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences  Shanghai China"},{"name":"School of Life Science and Technology ShanghaiTech University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyan","family":"He","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences  Shanghai China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Qi","family":"Xiong","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences  Shanghai China"},{"name":"School of Life Science and Technology ShanghaiTech University  Shanghai China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology Zhongshan Hospital, Fudan University  Shanghai China"},{"name":"The State Key Laboratory of Medical Neurobiology 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