{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:31:44Z","timestamp":1790713904410,"version":"4.1.0"},"reference-count":107,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T00:00:00Z","timestamp":1632873600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004794","name":"National Centre for Scientific Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"crossref"}]},{"name":"French National Institute of Health and Medical Research"},{"DOI":"10.13039\/501100003768","name":"University of Strasbourg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003768","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","award":["ANR-10-IDEX-0002-02, ANR-10-LABX-0030-INRT, ANR-10-INBS-07"],"award-info":[{"award-number":["ANR-10-IDEX-0002-02, ANR-10-LABX-0030-INRT, ANR-10-INBS-07"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fondation J\u00e9r\u00f4me Lejeune"},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["848077"],"award-info":[{"award-number":["848077"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    Perturbation of the excitation\/inhibition (E\/I) balance leads to neurodevelopmental diseases including to autism spectrum disorders, intellectual disability, and epilepsy. Loss-of-function mutations in the\n                    <jats:italic>DYRK1A<\/jats:italic>\n                    gene, located on human chromosome 21 (Hsa21,) lead to an intellectual disability syndrome associated with microcephaly, epilepsy, and autistic troubles. Overexpression of DYRK1A, on the other hand, has been linked with learning and memory defects observed in people with Down syndrome (DS).\n                    <jats:italic>Dyrk1a<\/jats:italic>\n                    is expressed in both glutamatergic and GABAergic neurons, but its impact on each neuronal population has not yet been elucidated. Here we investigated the impact of\n                    <jats:italic>Dyrk1a<\/jats:italic>\n                    gene copy number variation in glutamatergic neurons using a conditional knockout allele of\n                    <jats:italic>Dyrk1a<\/jats:italic>\n                    crossed with the Tg(Camk2-Cre)4Gsc transgenic mouse. We explored this genetic modification in homozygotes, heterozygotes and combined with the Dp(16\n                    <jats:italic>Lipi-Zbtb21<\/jats:italic>\n                    )1Yey trisomic mouse model to unravel the consequence of\n                    <jats:italic>Dyrk1a<\/jats:italic>\n                    dosage from 0 to 3, to understand its role in normal physiology, and in MRD7 and DS. Overall,\n                    <jats:italic>Dyrk1a<\/jats:italic>\n                    dosage in postnatal glutamatergic neurons did not impact locomotor activity, working memory or epileptic susceptibility, but revealed that\n                    <jats:italic>Dyrk1a<\/jats:italic>\n                    is involved in long-term explicit memory. Molecular analyses pointed at a deregulation of transcriptional activity through immediate early genes and a role of DYRK1A at the glutamatergic post-synapse by deregulating and interacting with key post-synaptic proteins implicated in mechanism leading to long-term enhanced synaptic plasticity. Altogether, our work gives important information to understand the action of DYRK1A inhibitors and have a better therapeutic approach.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1009777","type":"journal-article","created":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T14:22:08Z","timestamp":1632925328000},"page":"e1009777","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":37,"title":["Dyrk1a gene dosage in glutamatergic neurons has key effects in cognitive deficits observed in mouse models of MRD7 and Down syndrome"],"prefix":"10.1371","volume":"17","author":[{"given":"V\u00e9ronique","family":"Brault","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thu Lan","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5094-7978","authenticated-orcid":true,"given":"Javier","family":"Flores-Guti\u00e9rrez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Iacono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Christine","family":"Birling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Lalanne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4704-7055","authenticated-orcid":true,"given":"Hamid","family":"Meziane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antigoni","family":"Manousopoulou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9122-4592","authenticated-orcid":true,"given":"Guillaume","family":"Pavlovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7121-8857","authenticated-orcid":true,"given":"Lo\u00efc","family":"Lindner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Selloum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Sorg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8152-0790","authenticated-orcid":true,"given":"Eugene","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1050-0805","authenticated-orcid":true,"given":"Spiros 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