{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T12:53:44Z","timestamp":1782996824649,"version":"3.54.5"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012318","name":"International Max Planck Research School for Advanced Methods in Process and Systems Engineering","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012318","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Degeneration of hilar mossy cells in the dentate gyrus is an important hallmark of hippocampal sclerosis and is often observed in patients with temporal lobe epilepsy. To understand the pathogenesis of hippocampal sclerosis and develop novel neuroprotective treatments, it is critical to determine the mechanistic processes of mossy cell degeneration and factors that influence cell vulnerability or resilience. However, suitable in\u00a0vitro approaches are currently lacking. We have developed and validated an organotypic slice culture\u2010based in\u00a0vitro model that facilitates mechanistic studies of activity\u2010dependent mossy cell vulnerability and resilience.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A model was developed using entorhino\u2010hippocampal slice cultures. Dentate gyrus granule cells were transduced with adeno\u2010associated viruses to express channelrhodopsin2. Transduced cultures were chronically stimulated by light, and resulting cell damage was assessed by propidium iodide staining. Spontaneous synaptic activity before and after optical stimulation was recorded using whole\u2010cell patch\u2010clamp.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Selective and dose\u2010dependent hilar neuron degeneration was observed following chronic optogenetic stimulation of organotypic slice cultures expressing channelrhodopsin\u20102 in granule cells. Treatment with the anticonvulsant retigabine reduced stimulation\u2010induced hilar neuron loss in a dose\u2010dependent manner. This demonstrates the suitability of our optogenetic in\u00a0vitro model for drug screening. Patch\u2010clamp recordings verified strong synaptic activation of mossy cells during optical stimulation and a reduction in spontaneous excitatory synaptic activity after stimulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>The role of mossy cells in the context of epileptic seizures has been a controversial topic of discussion. The presented in\u00a0vitro model allows the study of mossy cell vulnerability on a single\u2010cell level and provides the first evidence for changes in synaptic activity after stimulation. This model will facilitate our mechanistic understanding of temporal lobe epilepsy, providing a foundation for novel therapeutic interventions aimed at preserving mossy cell function in epilepsy patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.18314","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T10:26:02Z","timestamp":1739355962000},"page":"1734-1746","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Chronic optogenetic stimulation of dentate gyrus granule cells in mouse organotypic slice cultures synaptically drives mossy cell degeneration"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6405-5514","authenticated-orcid":false,"given":"Carolin Christina","family":"Koretz","sequence":"first","affiliation":[{"name":"Institute for Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Fachbereich Medizin Goethe University Frankfurt  Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Schneider","sequence":"additional","affiliation":[{"name":"Institute for Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Fachbereich Medizin Goethe University Frankfurt  Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tassilo","family":"Jungenitz","sequence":"additional","affiliation":[{"name":"Institute for Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Fachbereich Medizin Goethe University Frankfurt  Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Drakew","sequence":"additional","affiliation":[{"name":"Institute for Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Fachbereich Medizin Goethe University Frankfurt  Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Roeper","sequence":"additional","affiliation":[{"name":"Institute of Neurophysiology, Fachbereich Medizin Goethe University Frankfurt  Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3931-2947","authenticated-orcid":false,"given":"Thomas","family":"Deller","sequence":"additional","affiliation":[{"name":"Institute for Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Fachbereich Medizin Goethe University Frankfurt  Frankfurt am Main 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