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Emerging evidence suggests their influence extends to seizure susceptibility, yet the underlying mechanisms remain unclear. Here, we investigated the functional role of PCs in locomotion and seizure\u2010like activity in zebrafish larvae. Using the UAS\/Gal4 system, we selectively expressed light\u2010sensitive ion channels in PCs: Channelrhodopsin\u20102 (ChR2) to activate, and Anion ChannelRhodopsin\u20102 (ACR2) to inhibit neuronal activity. Behavioral assays at 5\u2009days post\u2010fertilization assessed locomotor output, while local field potential recordings monitored seizure\u2010like events under baseline conditions and following administration of a proconvulsant agent. Optogenetic activation of PCs transiently increased locomotion and significantly reduced the duration and power of seizure\u2010like events under hyperexcitable conditions, without affecting baseline activity. Conversely, inhibition of PCs was sufficient to induce seizure\u2010like activity even in the absence of convulsant stimuli. These results reveal a dual role for PCs: they suppress pathological hyperexcitability during proconvulsant states, yet their inhibition can trigger seizures. This work highlights the cerebellum as a critical regulator of excitation\u2010inhibition balance, linking motor control and seizure susceptibility, and suggests that cerebellar dysfunction may contribute to both motor and epileptic phenotypes observed in neurodegenerative disorders.<\/jats:p>","DOI":"10.1002\/jnr.70118","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T04:35:07Z","timestamp":1770870907000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Purkinje Cells as Gatekeepers of Seizure Susceptibility: Insights From Optogenetics"],"prefix":"10.1002","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1759-5130","authenticated-orcid":false,"given":"Sara","family":"Bernardi","sequence":"first","affiliation":[{"name":"Neurobiology and Molecular Medicine Unit, IRCCS Fondazione Stella Maris  Pisa 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