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Although retrieval failure represents a hallmark of cognitive decline in AD, the task- and phase-specific molecular mechanisms underlying cholinergic-dependent memory retrieval remain poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study investigated whether acute muscarinic cholinergic blockade disrupts the retrieval phase of recognition memory. We also examined the associated regulation of hippocampal calcium\/calmodulin-dependent protein kinase II (CaMKII) isoforms \u03b1 and \u03b2, together with extracellular signal-regulated kinase (ERK) signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Adult male SWR\/J mice were trained in the NOR paradigm and administered scopolamine (1\u00a0mg\/kg, i.p.) or saline 30\u00a0min prior to the retrieval phase. Recognition memory performance was assessed using the discrimination index and exploratory preference. Immediately following behavioral testing, hippocampal tissue was collected for Western blot analysis of phosphorylated and total CaMKII-\u03b1, CaMKII-\u03b2, and ERK.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Scopolamine significantly impaired recognition memory retrieval, as evidenced by a reduced discrimination index and decreased preference for the novel object, without diminishing overall exploratory activity. At the molecular level, scopolamine-induced cholinergic inhibition selectively decreased hippocampal phosphorylation of both CaMKII-\u03b1 and CaMKII-\u03b2 while increasing ERK phosphorylation, with no significant changes in total protein expression of any kinase.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings identify a retrieval-specific, scopolamine-induced molecular signature of cholinergic inhibition in the hippocampus, characterized by concurrent suppression of both CaMKII isoform activities (\u03b1 and \u03b2) alongside dissociable ERK hyperactivation. By extending prior molecular observations from aversively motivated paradigms to an ethologically relevant model of recognition memory, this study provides mechanistic insight into how cholinergic dysfunction contributes to memory retrieval deficits and suggests that cholinergic signaling maintains the functional (CaMKII-\u03b1) and structural (CaMKII-\u03b2) dimensions of hippocampal memory retrieval machinery through coordinated kinase activation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12868-026-01027-0","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:52:20Z","timestamp":1784555540000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cholinergic inhibition disrupts retrieval-specific phosphorylation of CaMKII-\u03b1 and CaMKII-\u03b2 alongside ERK hyperactivation in the hippocampus during novel object recognition memory"],"prefix":"10.1186","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1252-3215","authenticated-orcid":false,"given":"Majid Reza","family":"Farrokhi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5092-7854","authenticated-orcid":false,"given":"Alireza","family":"Askari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5364-8458","authenticated-orcid":false,"given":"Roksana","family":"SoukhakLari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6943-477X","authenticated-orcid":false,"given":"Maryam","family":"Moosavi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"1027_CR1","doi-asserted-by":"publisher","unstructured":"Soncu B\u00fcy\u00fcki\u015fcan E. 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The present article does not contain any experiments on human participants.","order":1,"name":"Ethics","label":"Ethical Statement","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"44"}}