{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:00:09Z","timestamp":1789988409082,"version":"4.0.1"},"reference-count":54,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"Brain Science and Brain-like Intelligence Technology\u2014National Science and Technology Major Project","doi-asserted-by":"publisher","award":["2021ZD0201003"],"award-info":[{"award-number":["2021ZD0201003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31830035"],"award-info":[{"award-number":["31830035"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32171092"],"award-info":[{"award-number":["32171092"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["31830035"],"award-info":[{"award-number":["31830035"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["32171092"],"award-info":[{"award-number":["32171092"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Shenzhen Science and Technology Program","doi-asserted-by":"publisher","award":["JCYJ20220530154402005"],"award-info":[{"award-number":["JCYJ20220530154402005"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shenzhen Key Laboratory of Viral Vectors for Biomedicine","award":["ZDSYS20200811142401005"],"award-info":[{"award-number":["ZDSYS20200811142401005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Optogenetic manipulation is pivotal in basic neuroscience research and in studying neuropsychiatric disorders, enabling the activation or inhibition of neuronal populations with millisecond precision. However, this technique can induce artificial neuronal hypersynchronization that is rarely observed under physiological conditions. Given that epileptic seizures arise from abnormally synchronized neuronal discharges, the potential for optogenetic stimulation to trigger seizures and confound experimental outcomes warrants close examination. Here, using electrophysiological and behavioral recordings, we demonstrate that even single-trial optogenetic stimulation of CaMKII-positive neurons in the hippocampal CA1 region, anterior piriform cortex (APC), or lateral\/medial entorhinal cortex (LEnt or MEnt) can induce seizure-like discharges and behaviors in adult male C57BL\/6 mice. Repeated stimulation in the APC, LEnt, or MEnt elicited more severe seizure-like activity. Furthermore, stimulation protocols characterized by high power, long duration, high frequency, and medium pulse width were more prone to inducing such events. Additionally, we found that CA1 stimulation could impair subsequent contextual fear memory. These findings provide critical cautions and practical guidelines for the design and implementation of in vivo optogenetic experiments in neuroscience research.<\/jats:p>","DOI":"10.3390\/biology15181669","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:01:38Z","timestamp":1789981298000},"page":"1669","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Seizure-Inducible Risks of In Vivo Optogenetic Manipulations"],"prefix":"10.3390","volume":"15","author":[{"given":"Xutao","family":"Zhu","sequence":"first","affiliation":[{"name":"Shenzhen Key Laboratory of Viral Vectors for Biomedicine, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"},{"name":"State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Center for Magnetic Resonance, Innovation Academy for 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China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Liping","family":"Wang","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Viral Vectors for Biomedicine, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"},{"name":"Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5774-7397","authenticated-orcid":false,"given":"Qing","family":"Liu","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Viral Vectors for Biomedicine, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institutes of Advanced 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