{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:48:08Z","timestamp":1791330488798,"version":"4.3.1"},"reference-count":55,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,6,20]],"date-time":"2017-06-20T00:00:00Z","timestamp":1497916800000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS058585"],"award-info":[{"award-number":["NS058585"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001605","name":"Epilepsy Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001605","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To understand how monosynaptic inputs onto adult\u2010born dentate granule cells (DGCs) are altered in experimental mesial temporal lobe epilepsy (mTLE) and whether their integration differs from early\u2010born DGCs that are mature at the time of epileptogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A dual\u2010virus tracing strategy combining retroviral birthdating with rabies virus\u2010mediated putative retrograde trans\u2010synaptic tracing was used to identify and compare presynaptic inputs onto adult\u2010born and early\u2010born DGCs in the rat pilocarpine model of mTLE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results demonstrate that hilar ectopic DGCs preferentially synapse onto adult\u2010born DGCs after pilocarpine\u2010induced status epilepticus (SE), whereas normotopic DGCs synapse onto both adult\u2010born and early\u2010born DGCs. We also find that parvalbumin<jats:sup>\u2212<\/jats:sup> and somatostatin<jats:sup>\u2212<\/jats:sup> interneuron inputs are greatly diminished onto early\u2010born DGCs after SE. However, somatostatin<jats:sup>\u2212<\/jats:sup> interneuron inputs onto adult\u2010born DGCs are maintained, likely due to preferential sprouting. Intriguingly, CA3 pyramidal cell backprojections that specifically target adult\u2010born DGCs arise in the epileptic brain, whereas axons of interneurons and pyramidal cells in CA1 appear to sprout across the hippocampal fissure to preferentially synapse onto early\u2010born DGCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>These data support the presence of substantial hippocampal circuit remodeling after an epileptogenic insult that generates prominent excitatory monosynaptic inputs, both local recurrent and widespread feedback loops, onto DGCs. Both adult\u2010born and early\u2010born DGCs are targets of new inputs from other DGCs as well as from CA3 and CA1 pyramidal cells after pilocarpine treatment, changes that likely contribute to epileptogenesis in experimental mTLE. 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