{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:17:04Z","timestamp":1772173024921,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1010239","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T00:00:00Z","timestamp":1657238400000}}],"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T00:00:00Z","timestamp":1656288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS102490"],"award-info":[{"award-number":["NS102490"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["MH065635"],"award-info":[{"award-number":["MH065635"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Key features of long-term memory (LTM), such as its stability and persistence, are acquired during processes collectively referred to as consolidation. The dynamics of biological changes during consolidation are complex. In adult rodents, consolidation exhibits distinct periods during which the engram is more or less resistant to disruption. Moreover, the ability to consolidate memories differs during developmental periods. Although the molecular mechanisms underlying consolidation are poorly understood, the initial stages rely on interacting signaling pathways that regulate gene expression, including brain-derived neurotrophic factor (BDNF) and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \/calmodulin-dependent protein kinase II \u03b1 (CaMKII\u03b1) dependent feedback loops. We investigated the ways in which these pathways may contribute to developmental and dynamical features of consolidation. A computational model of molecular processes underlying consolidation following inhibitory avoidance (IA) training in rats was developed. Differential equations described the actions of CaMKII\u03b1, multiple feedback loops regulating BDNF expression, and several transcription factors including methyl-CpG binding protein 2 (MeCP2), histone deacetylase 2 (HDAC2), and SIN3 transcription regulator family member A (Sin3a). This model provides novel explanations for the (apparent) rapid forgetting of infantile memory and the temporal progression of memory consolidation in adults. Simulations predict that dual effects of MeCP2 on the expression of\n                    <jats:italic>bdnf<\/jats:italic>\n                    , and interaction between MeCP2 and CaMKII\u03b1, play critical roles in the rapid forgetting of infantile memory and the progress of memory resistance to disruptions. These insights suggest new potential targets of therapy for memory impairment.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1010239","type":"journal-article","created":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T13:36:30Z","timestamp":1656336990000},"page":"e1010239","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Computational analysis of memory consolidation following inhibitory avoidance (IA) training in adult and infant rats: Critical roles of CaMKII\u03b1 and MeCP2"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2591-1324","authenticated-orcid":true,"given":"Yili","family":"Zhang","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7762-8096","authenticated-orcid":true,"given":"Paul","family":"Smolen","sequence":"additional","affiliation":[]},{"given":"Cristina M.","family":"Alberini","sequence":"additional","affiliation":[]},{"given":"Douglas A.","family":"Baxter","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7947-5890","authenticated-orcid":true,"given":"John H.","family":"Byrne","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2022,6,27]]},"reference":[{"key":"pcbi.1010239.ref001","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/S0959-4388(00)00194-X","article-title":"Molecular mechanisms of memory acquisition, consolidation and retrieval","volume":"11","author":"T Abel","year":"2001","journal-title":"Curr. 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