{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:20:42Z","timestamp":1790824842638,"version":"4.1.0"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"33","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G00C9922N"],"award-info":[{"award-number":["G00C9922N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G0F0414N"],"award-info":[{"award-number":["G0F0414N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004497","name":"Onderzoeksraad, KU Leuven","doi-asserted-by":"publisher","award":["C14\/20\/071"],"award-info":[{"award-number":["C14\/20\/071"]}],"id":[{"id":"10.13039\/501100004497","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004497","name":"Onderzoeksraad, KU Leuven","doi-asserted-by":"publisher","award":["KA\/20\/013"],"award-info":[{"award-number":["KA\/20\/013"]}],"id":[{"id":"10.13039\/501100004497","id-type":"DOI","asserted-by":"publisher"}]},{"name":"EASI-Genomics - European Union\u2019s Horizon 2020 research and innovation program","award":["No 824110"],"award-info":[{"award-number":["No 824110"]}]},{"DOI":"10.13039\/501100004040","name":"KU Leuven","doi-asserted-by":"publisher","award":["VTI-23-00197"],"award-info":[{"award-number":["VTI-23-00197"]}],"id":[{"id":"10.13039\/501100004040","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":[[2026,8,18]]},"abstract":"<jats:p>Successful repair after brain injury requires a chain of events, including the generation, migration, and successful integration of adult-born neurons into preexisting circuits. In mammals, the capacity for neuronal regeneration is extremely limited and further declines with age, constraining recovery. Regeneration-competent vertebrates offer a unique opportunity to uncover mechanistic principles of seamless brain repair. We here introduce the African turquoise killifish, a naturally short-lived vertebrate in which tissue repair occurs at young but not old age. We established an integrative approach combining i) an optimized retroviral vector application to birthdate GFP-labeled dividing neural stem cells and their progeny, ii) targeted electrophysiology to quantify synaptic and intrinsic maturation of such neurons, and iii) a conditioned avoidance assay to track recovery of learned behavior in adult killifish. We applied this workflow to the dorsomedial telencephalon, a region homologous to the mammalian amygdala. We reveal that injury-induced adult-born neurons survive, mature, and integrate synaptically into preexisting circuits, and that this coincides with the recovery of learned avoidance behavior by two months postinjury. Only when newborn neurons display mature morpho-electric properties, including complex dendritic arborization and abundant dendritic spines, recovery of behavior is accomplished. That full functional recovery takes around 50 d, substantially longer than previously inferred from histological analyses alone, is a striking finding given the killifish\u2019s short lifespan. These findings establish the killifish as a powerful vertebrate model and introduce a scalable platform for experimentally manipulating neuronal maturation and integration in vivo, particularly in the context of aging and age-related regenerative decline.<\/jats:p>","DOI":"10.1073\/pnas.2607510123","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T19:09:16Z","timestamp":1786388956000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["Morphological maturation and circuit integration of adult-born neurons are key to functional recovery after traumatic brain injury"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7749-8199","authenticated-orcid":false,"given":"Valerie","family":"Mari\u00ebn","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f950310","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Neuroplasticity and Neuroproteomics, Division of Animal Physiology and Neurobiology, Department of Biology, KU Leuven","place":["Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Zandecki","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f950310","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Neuroplasticity and Neuroproteomics, Division of Animal Physiology and Neurobiology, Department of Biology, KU Leuven","place":["Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5072-6729","authenticated-orcid":false,"given":"Jolien","family":"Van houcke","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f950310","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Neuroplasticity and Neuroproteomics, Division of Animal Physiology and Neurobiology, Department of Biology, KU Leuven","place":["Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anouk","family":"Maes","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f950310","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Neuroplasticity and Neuroproteomics, Division of Animal Physiology and Neurobiology, Department of Biology, KU Leuven","place":["Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajagopal","family":"Ayana","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f950310","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Neuroplasticity and Neuroproteomics, Division of Animal Physiology and Neurobiology, Department of Biology, KU Leuven","place":["Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Van den Haute","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f950310","id-type":"ROR","asserted-by":"publisher"}],"name":"Leuven Viral Vector Core, Group Biomedical Sciences, KU Leuven","place":["Leuven, Belgium"]},{"id":[{"id":"https:\/\/ror.org\/05f950310","id-type":"ROR","asserted-by":"publisher"}],"name":"Research Group for Neurobiology and Gene Therapy, Department of Neuroscience, KU Leuven","place":["Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0191-3904","authenticated-orcid":false,"given":"Rik","family":"Gijsbers","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f950310","id-type":"ROR","asserted-by":"publisher"}],"name":"Leuven Viral Vector Core, Group Biomedical Sciences, KU Leuven","place":["Leuven, Belgium"]},{"id":[{"id":"https:\/\/ror.org\/05f950310","id-type":"ROR","asserted-by":"publisher"}],"name":"Advanced Disease Modelling, Targeted Drug Discovery and Gene Therapy Research Group, Department of Pharmacological and Pharmaceutical Sciences, Group Biomedical Sciences, KU Leuven","place":["Leuven, Belgium"]},{"id":[{"id":"https:\/\/ror.org\/05f950310","id-type":"ROR","asserted-by":"publisher"}],"name":"Leuven Institute for Rare Diseases","place":["Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3183-2689","authenticated-orcid":false,"given":"Marialuisa","family":"Tognolina","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f950310","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Neuroplasticity and Neuroproteomics, Division of Animal Physiology and Neurobiology, Department of Biology, KU Leuven","place":["Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2909-8449","authenticated-orcid":false,"given":"Lutgarde","family":"Arckens","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f950310","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratory of Neuroplasticity and Neuroproteomics, Division of Animal Physiology and Neurobiology, Department of Biology, KU Leuven","place":["Leuven, Belgium"]},{"id":[{"id":"https:\/\/ror.org\/05f950310","id-type":"ROR","asserted-by":"publisher"}],"name":"Leuven Brain Institute, KU Leuven","place":["Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/biosci\/biw079"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2014.00092"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-03-00629.2002"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1340"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0056-15.2015"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm747"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep21793"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2009.10.008"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-017-0033-9"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1242\/bio.061984"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.226357"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13464"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.058156"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4930-03.2004"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/ar.22668"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-1-4160-4252-5.50041-1"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14251"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2019.12.046"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.072587"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa2729"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.22710"},{"key":"e_1_3_4_22_2","article-title":"Triggering reactive gliosis in vivo by a forebrain stab injury","volume":"100","author":"Allahyari R. V.","year":"2015","unstructured":"R. V. Allahyari, A. D. R. Garcia, Triggering reactive gliosis in vivo by a forebrain stab injury. J. Vis. Exp. 100, e52825 (2015).","journal-title":"J. Vis. Exp."},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22269"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells10020391"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.007336"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4930-03.2004"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-018-0502-y"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1159\/000113278"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.beproc.2016.08.009"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/ece3.4356"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2009.42.5.245"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3240-08.2008"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4785-12.2013"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.10.002"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/4151030a"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000126480.40967.b3"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.87527"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2010281117"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4301"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/336468a0"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature00850"},{"key":"e_1_3_4_42_2","first-page":"78","article-title":"Morphological status of multipolar neurons in the lateral cortical area of the telencephalon of a catfish, clarias batrachus: A golgi study","volume":"9","author":"Mohanty B.","year":"2021","unstructured":"B. Mohanty, A. K. Ojha, Morphological status of multipolar neurons in the lateral cortical area of the telencephalon of a catfish, clarias batrachus: A golgi study. J. Appl. Biol. Biotechnol. 9, 78\u201382 (2021).","journal-title":"J. Appl. Biol. Biotechnol."},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.049507"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.23097"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature20113"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2607510123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T19:11:28Z","timestamp":1786389088000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2607510123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,10]]},"references-count":45,"journal-issue":{"issue":"33","published-print":{"date-parts":[[2026,8,18]]}},"alternative-id":["10.1073\/pnas.2607510123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2607510123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,10]]},"assertion":[{"value":"2026-03-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2607510123"}}