{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:20:09Z","timestamp":1790619609987,"version":"4.1.0"},"reference-count":63,"publisher":"National Academy of Sciences","issue":"32","license":[{"start":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T00:00:00Z","timestamp":1659657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01-NS113600"],"award-info":[{"award-number":["R01-NS113600"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"HHS | NIH | National Institute of Mental Health","doi-asserted-by":"publisher","award":["R01-MH125772"],"award-info":[{"award-number":["R01-MH125772"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01-NS115443"],"award-info":[{"award-number":["R01-NS115443"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"HHS | NIH | National Institute of Mental Health","doi-asserted-by":"publisher","award":["R01-MH116673"],"award-info":[{"award-number":["R01-MH116673"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"HHS | NIH | National Institute of Mental Health","doi-asserted-by":"publisher","award":["R21-MH120496"],"award-info":[{"award-number":["R21-MH120496"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,8,9]]},"abstract":"<jats:p>\n                    Epilepsy is a devastating brain disorder for which effective treatments are very limited. There is growing interest in early intervention, which requires a better mechanistic understanding of the early stages of this disorder. While diverse brain insults can lead to epileptic activity, a common cellular mechanism relies on uncontrolled recurrent excitatory activity. In the dentate gyrus, excitatory mossy cells (MCs) project extensively onto granule cells (GCs) throughout the hippocampus, thus establishing a recurrent MC-GC-MC excitatory loop. MCs are implicated in temporal lobe epilepsy, a common form of epilepsy, but their role during initial seizures (i.e., before the characteristic MC loss that occurs in late stages) is unclear. Here, we show that initial seizures acutely induced with an intraperitoneal kainic acid (KA) injection in adult mice, a well-established model that leads to experimental epilepsy, not only increased MC and GC activity in\u00a0vivo but also triggered a brain-derived neurotrophic factor (BDNF)\u2013dependent long-term potentiation (LTP) at MC-GC excitatory synapses. Moreover, in\u00a0vivo induction of MC-GC LTP using MC-selective optogenetic stimulation worsened KA-induced seizures. Conversely,\n                    <jats:italic>Bdnf<\/jats:italic>\n                    genetic removal from GCs, which abolishes LTP, and selective MC silencing were both anticonvulsant. Thus, initial seizures are associated with MC-GC synaptic strengthening, which may promote later epileptic activity. Our findings reveal a potential mechanism of epileptogenesis that may help in developing therapeutic strategies for early intervention.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2201151119","type":"journal-article","created":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T14:10:36Z","timestamp":1659708636000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":37,"title":["Seizure-induced strengthening of a recurrent excitatory circuit in the dentate gyrus is proconvulsant"],"prefix":"10.1073","volume":"119","author":[{"given":"Kaoutsar","family":"Nasrallah","sequence":"first","affiliation":[{"name":"Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9889-306X","authenticated-orcid":false,"given":"M. Agustina","family":"Frechou","sequence":"additional","affiliation":[{"name":"Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461"},{"name":"Gottesman Institute for Stem Cell Biology and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, NY 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young J.","family":"Yoon","sequence":"additional","affiliation":[{"name":"Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461"},{"name":"Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1386-7565","authenticated-orcid":false,"given":"Subrina","family":"Persaud","sequence":"additional","affiliation":[{"name":"Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Tiago","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461"},{"name":"Gottesman Institute for Stem Cell Biology and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, NY 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9834-1801","authenticated-orcid":false,"given":"Pablo E.","family":"Castillo","sequence":"additional","affiliation":[{"name":"Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461"},{"name":"Department of Psychiatry &amp; Behavioral Sciences, Albert Einstein College of Medicine, Bronx, NY 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,8,5]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12550"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13634"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2016.87"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan4074"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.10.100"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra022308"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.10.036"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(00)02122-6"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.2000.tb01577.x"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/89.3.499"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.3171\/2008.11.JNS08779"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2006.00602.x"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-21-09519.1999"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.06.083"},{"key":"e_1_3_4_15_2","first-page":"583","article-title":"Cellular basis of neuronal synchrony in epilepsy","volume":"44","author":"Wong R. 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