{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:22:02Z","timestamp":1790814122397,"version":"4.1.0"},"reference-count":88,"publisher":"Society for Neuroscience","issue":"18","license":[{"start":{"date-parts":[[2016,11,4]],"date-time":"2016-11-04T00:00:00Z","timestamp":1478217600000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2016,5,4]]},"abstract":"<jats:p>\n                    During hippocampal development, newly born neurons migrate to appropriate destinations, extend axons, and ramify dendritic arbors to establish functional circuitry. These developmental stages are recapitulated in the dentate gyrus of the adult hippocampus, where neurons are continuously generated and subsequently incorporate into existing, local circuitry. Here we demonstrate that the E3 ubiquitin ligase TRIM9 regulates these developmental stages in embryonic and adult-born mouse hippocampal neurons\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Embryonic hippocampal and adult-born dentate granule neurons lacking\n                    <jats:italic>Trim9<\/jats:italic>\n                    exhibit several morphological defects, including excessive dendritic arborization. Although gross anatomy of the hippocampus was not detectably altered by\n                    <jats:italic>Trim9<\/jats:italic>\n                    deletion, a significant number of\n                    <jats:italic>Trim9<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    adult-born dentate neurons localized inappropriately. These morphological and localization defects of hippocampal neurons in\n                    <jats:italic>Trim9<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice were associated with extreme deficits in spatial learning and memory, suggesting that TRIM9-directed neuronal morphogenesis may be involved in hippocampal-dependent behaviors.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>SIGNIFICANCE STATEMENT<\/jats:bold>\n                    Appropriate generation and incorporation of adult-born neurons in the dentate gyrus are critical for spatial learning and memory and other hippocampal functions. Here we identify the brain-enriched E3 ubiquitin ligase TRIM9 as a novel regulator of embryonic and adult hippocampal neuron shape acquisition and hippocampal-dependent behaviors. Genetic deletion of\n                    <jats:italic>Trim9<\/jats:italic>\n                    elevated dendritic arborization of hippocampal neurons\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Adult-born dentate granule cells lacking\n                    <jats:italic>Trim9<\/jats:italic>\n                    similarly exhibited excessive dendritic arborization and mislocalization of cell bodies\n                    <jats:italic>in vivo<\/jats:italic>\n                    . These cellular defects were associated with severe deficits in spatial learning and memory.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.3876-15.2016","type":"journal-article","created":{"date-parts":[[2016,5,4]],"date-time":"2016-05-04T13:52:48Z","timestamp":1462369968000},"page":"4940-4958","source":"Crossref","is-referenced-by-count":63,"title":["<i>Trim9<\/i>\n                    Deletion Alters the Morphogenesis of Developing and Adult-Born Hippocampal Neurons and Impairs Spatial Learning and Memory"],"prefix":"10.1523","volume":"36","author":[{"given":"Cortney C.","family":"Winkle","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reid H. J.","family":"Olsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyojin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheryl S.","family":"Moy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie L.","family":"Gupton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2016,5,4]]},"reference":[{"key":"2023041803185705000_36.18.4940.1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.469"},{"key":"2023041803185705000_36.18.4940.2","doi-asserted-by":"crossref","first-page":"4797","DOI":"10.1242\/dev.127.22.4797","article-title":"Aberrant development of hippocampal circuits and altered neural activity in netrin 1-deficient mice","volume":"127","author":"Barallobre","year":"2000","journal-title":"Development"},{"key":"2023041803185705000_36.18.4940.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(02)00013-8"},{"key":"2023041803185705000_36.18.4940.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.07.028"},{"key":"2023041803185705000_36.18.4940.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2006.12.008"},{"key":"2023041803185705000_36.18.4940.6","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22397"},{"key":"2023041803185705000_36.18.4940.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(00)00124-0"},{"key":"2023041803185705000_36.18.4940.8","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0024 16.2016"},{"key":"2023041803185705000_36.18.4940.9","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-071013-014134"},{"key":"2023041803185705000_36.18.4940.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.11.016"},{"key":"2023041803185705000_36.18.4940.11","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3362-09.2009"},{"key":"2023041803185705000_36.18.4940.12","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2822"},{"key":"2023041803185705000_36.18.4940.13","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a001800"},{"key":"2023041803185705000_36.18.4940.14","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1523\/JNEUROSCI.08-04-01454.1988","article-title":"The establishment of polarity by hippocampal neurons in culture","volume":"8","author":"Dotti","year":"1988","journal-title":"J Neurosci"},{"key":"2023041803185705000_36.18.4940.15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001959"},{"key":"2023041803185705000_36.18.4940.16","doi-asserted-by":"publisher","DOI":"10.1038\/386796a0"},{"key":"2023041803185705000_36.18.4940.17","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)00084-2"},{"key":"2023041803185705000_36.18.4940.18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024566"},{"key":"2023041803185705000_36.18.4940.19","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(91)90299-4"},{"key":"2023041803185705000_36.18.4940.20","first-page":"155","article-title":"Prenatal morphine exposure reduces pyramidal neurons in CA1, CA2 and CA3 subfields of mice hippocampus","volume":"17","author":"Ghafari","year":"2014","journal-title":"Iranian J Basic Med Sci"},{"key":"2023041803185705000_36.18.4940.21","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20256"},{"key":"2023041803185705000_36.18.4940.22","doi-asserted-by":"publisher","DOI":"10.1038\/nature02033"},{"key":"2023041803185705000_36.18.4940.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2010.02.017"},{"key":"2023041803185705000_36.18.4940.24","doi-asserted-by":"publisher","DOI":"10.1038\/nn923"},{"key":"2023041803185705000_36.18.4940.25","doi-asserted-by":"publisher","DOI":"10.1667\/RR2946.1"},{"key":"2023041803185705000_36.18.4940.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2010.02.019"},{"key":"2023041803185705000_36.18.4940.27","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3139"},{"key":"2023041803185705000_36.18.4940.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2012.09.019"},{"key":"2023041803185705000_36.18.4940.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2013.12.016"},{"key":"2023041803185705000_36.18.4940.30","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M400045-MCP200"},{"key":"2023041803185705000_36.18.4940.31","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.32164"},{"key":"2023041803185705000_36.18.4940.32","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/10.10.981"},{"key":"2023041803185705000_36.18.4940.33","doi-asserted-by":"publisher","DOI":"10.1038\/nn1847"},{"key":"2023041803185705000_36.18.4940.34","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00857-14"},{"key":"2023041803185705000_36.18.4940.35","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e31829ecc89"},{"key":"2023041803185705000_36.18.4940.36","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(04)00108-4"},{"key":"2023041803185705000_36.18.4940.37","doi-asserted-by":"crossref","first-page":"6434","DOI":"10.1523\/JNEUROSCI.17-16-06434.1997","article-title":"Role of the hippocampus, the bed nucleus of the stria terminalis, and the amygdala in the excitatory effect of corticotropin-releasing hormone on the acoustic startle reflex","volume":"17","author":"Lee","year":"1997","journal-title":"J Neurosci"},{"key":"2023041803185705000_36.18.4940.38","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M106141200"},{"key":"2023041803185705000_36.18.4940.39","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.129841"},{"key":"2023041803185705000_36.18.4940.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2014.06.013"},{"key":"2023041803185705000_36.18.4940.41","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2011.07897.x"},{"key":"2023041803185705000_36.18.4940.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2015.11.022"},{"key":"2023041803185705000_36.18.4940.43","first-page":"183","article-title":"The Building Blocks of a Functioning Brain: Cytoskeletal Dynamics in Neuronal Development. International Review of Cell and Molecular Biology","volume":"Vol. 322","author":"Menon","year":"2016","journal-title":"Elsevier Academic Press"},{"key":"2023041803185705000_36.18.4940.44","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1200935"},{"key":"2023041803185705000_36.18.4940.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.05.001"},{"key":"2023041803185705000_36.18.4940.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2012.11.019"},{"key":"2023041803185705000_36.18.4940.47","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1109843108"},{"key":"2023041803185705000_36.18.4940.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2008.03.015"},{"key":"2023041803185705000_36.18.4940.49","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2008.00452.x"},{"key":"2023041803185705000_36.18.4940.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2009.06.021"},{"key":"2023041803185705000_36.18.4940.51","doi-asserted-by":"publisher","DOI":"10.1002\/iub.580"},{"key":"2023041803185705000_36.18.4940.52","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1861"},{"key":"2023041803185705000_36.18.4940.53","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2012.00833.x"},{"key":"2023041803185705000_36.18.4940.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2013.08.015"},{"key":"2023041803185705000_36.18.4940.55","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12187"},{"key":"2023041803185705000_36.18.4940.56","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2741"},{"key":"2023041803185705000_36.18.4940.57","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2005.06.028"},{"key":"2023041803185705000_36.18.4940.58","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2593"},{"key":"2023041803185705000_36.18.4940.59","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.08.002"},{"key":"2023041803185705000_36.18.4940.60","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2014.09.010"},{"key":"2023041803185705000_36.18.4940.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2013.12.005"},{"key":"2023041803185705000_36.18.4940.62","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001997"},{"key":"2023041803185705000_36.18.4940.63","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"2023041803185705000_36.18.4940.64","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81795-X"},{"key":"2023041803185705000_36.18.4940.65","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90420-0"},{"key":"2023041803185705000_36.18.4940.66","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3065"},{"key":"2023041803185705000_36.18.4940.67","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20525"},{"key":"2023041803185705000_36.18.4940.68","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3572"},{"key":"2023041803185705000_36.18.4940.69","doi-asserted-by":"crossref","unstructured":"Song J Olsen RH Sun J Ming G Song H (2015) Neuronal circuitry mechanisms regulating adult mammalian neurogenesis. Cold Spring Harb Perspect Biol, 289\u2013308, 10.1101\/cshperspect.a018937.","DOI":"10.1101\/cshperspect.a018937"},{"key":"2023041803185705000_36.18.4940.70","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.20907"},{"key":"2023041803185705000_36.18.4940.71","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2286"},{"key":"2023041803185705000_36.18.4940.72","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3100-11.2011"},{"key":"2023041803185705000_36.18.4940.73","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.01.007"},{"key":"2023041803185705000_36.18.4940.74","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00067"},{"key":"2023041803185705000_36.18.4940.75","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2015.293"},{"key":"2023041803185705000_36.18.4940.76","doi-asserted-by":"publisher","DOI":"10.3791\/2373"},{"key":"2023041803185705000_36.18.4940.77","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntt.2014.07.003"},{"key":"2023041803185705000_36.18.4940.78","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201405026"},{"key":"2023041803185705000_36.18.4940.79","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1523\/JNEUROSCI.21-03-00983.2001","article-title":"Abnormal morphological and functional organization of the hippocampus in a p35 mutant model of cortical dysplasia associated with spontaneous seizures","volume":"21","author":"Wenzel","year":"2001","journal-title":"J Neurosci"},{"key":"2023041803185705000_36.18.4940.80","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201311003"},{"key":"2023041803185705000_36.18.4940.81","first-page":"247","article-title":"The Ins and Outs of Neural Connectivity Membrane Trafficking in Neuronal Development. International Review of Cell and Molecular Biology","volume":"Vol. 322","author":"Winkle","year":"2016","journal-title":"Elsevier Academic Press"},{"key":"2023041803185705000_36.18.4940.82","doi-asserted-by":"publisher","DOI":"10.1101\/lm.725207"},{"key":"2023041803185705000_36.18.4940.83","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1063(1999)9:6<668::AID-HIPO8>3.0.CO;2-9"},{"key":"2023041803185705000_36.18.4940.84","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00146"},{"key":"2023041803185705000_36.18.4940.85","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20409"},{"key":"2023041803185705000_36.18.4940.86","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2014.03.041"},{"key":"2023041803185705000_36.18.4940.87","doi-asserted-by":"publisher","DOI":"10.1242\/dev.128942"},{"key":"2023041803185705000_36.18.4940.88","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.12.033"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.3876-15.2016","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T06:32:10Z","timestamp":1681799530000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.3876-15.2016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,4]]},"references-count":88,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2016,5,4]]},"published-print":{"date-parts":[[2016,5,4]]}},"alternative-id":["10.1523\/JNEUROSCI.3876-15.2016"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.3876-15.2016","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,4]]}}}