ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026
Reciprocal molecular and cellular cholinergic working memory impairments in Alzheimer's disease model mice.
Chloe I Rybicki-Kler, Isla A W Brooks, Izabela Jedrasiak-Cape, Tao Deng, Cassandra Avila, Elizabeth Brouns, Alex Lekander, Omar J Ahmed
Abstract read
In one paragraphArticle in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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2 · The registryThe trial behind it
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5 · Who and what moneyAuthors and funding
8 authors.
Chloe I Rybicki-KlerDepartment of Psychology, University of Michigan, Ann Arbor, Michigan, USA.
Isla A W BrooksDepartment of Psychology, University of Michigan, Ann Arbor, Michigan, USA.
Izabela Jedrasiak-CapeDepartment of Psychology, University of Michigan, Ann Arbor, Michigan, USA.
Tao DengDepartment of Psychology, University of Michigan, Ann Arbor, Michigan, USA.
Cassandra AvilaDepartment of Psychology, University of Michigan, Ann Arbor, Michigan, USA.
Elizabeth BrounsDepartment of Psychology, University of Michigan, Ann Arbor, Michigan, USA.
Alex LekanderDepartment of Psychology, University of Michigan, Ann Arbor, Michigan, USA.
Funding
Research Education ComponentP30AG072931 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Henry L Paulson · 2021 to 2026
$26.5MUdall Catalyst Research Project: Retrosplenial Cholinergic and Attentional-Motor Integration DysfunctionP50NS123067 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALBIN, ROGER L · 2021 to 2025
$11.6MSensory Mechanisms and Disorders - Administrative SupplementT32DC000011 · NIDCD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Michael Thomas Roberts · 1989 to 2026
$9.5MTRAINING IN CLINICAL AND BASIC NEUROSCIENCET32NS007222 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Henry L Paulson · 1985 to 2026
$8.0MEarly Stage Training in the NeurosciencesT32NS076401 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Carol Fuzeti Elias, LESLIE S. SATIN · 2011 to 2026
$3.1MCircuit Mechanisms of Psilocybin Following Chronic StressR01MH129282 · NIMH · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Omar Jamil Ahmed · 2022 to 2026
$1.9MEnabling precise cell-type-specific dissection of orientation and memory circuits in retrosplenial cortexR34NS127101 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI AHMED, OMAR JAMIL · 2022 to 2022
$679kCell-type-specific dissection of retrosplenial circuits in preclinical models of Alzheimer's diseaseF31AG087629 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI RYBICKI-KLER, CHLOE ISABELLA · 2024 to 2025
$86kAlzheimer's Association AARG-NTF-21-846572Berger Endowment G102865/321033NIA NIH HHS F31 AG087629NIA NIH HHS F31AG087629NIA NIH HHS P30 AG072931NIA NIH HHS P30AG072931NIDCD NIH HHS T32 DC000011NIDCD NIH HHS T32DC000011NIMH NIH HHS R01 MH129282NIMH NIH HHS R01MH129282NINDS NIH HHS P50 NS123067NINDS NIH HHS P50NS123067NINDS NIH HHS R34 NS127101NINDS NIH HHS R34NS127101NINDS NIH HHS T32 NS007222NINDS NIH HHS T32NS007222NINDS NIH HHS T32 NS076401NINDS NIH HHS T32NS076401
6 · The paper itselfAbstract
introductionThe degeneration of basal forebrain cholinergic neurons is a key pathophysiological feature of Alzheimer's disease (AD). These cholinergic neurons target cortical neurons including those in the granular retrosplenial cortex (RSG) to facilitate essential cognitive functions. At the cellular level, acetylcholine supports working memory by inducing persistent firing that outlasts the stimulus, but how such cholinergic-induced persistent firing is altered in AD remains unknown.
methodsUsing multiscale molecular and cellular analyses, we investigated neuron type-specific transcriptomic and physiological impairments of cholinergic persistent signaling in the RSG of 5xFAD mice.
resultsCholinergic inputs to RSG were reduced in 5xFAD mice. Expression of the Chrm1 gene encoding M1 muscarinic receptors was also reduced in RSG neurons, coupled with impaired cellular persistent firing. DISCUSSION: The loss of M1 receptors suggests that allosteric M1 modulators being considered for treatment of AD symptoms may not be as effective on key cell types, necessitating further multiscale investigation.
Indexed as
Alzheimer DiseaseCholinergic NeuronsMemory DisordersMemory, Short-TermReceptor, Muscarinic M1AcetylcholineAnimalsDisease Models, AnimalHumansMiceMice, TransgenicAcetylcholineReceptor, Muscarinic M1acetylcholineafter depolarizationCalcium‐activated non‐selective cation current (ICAN)carbacholcognitiong proteingranular retrosplenial cortexM1 receptorsmemorymuscarinic receptorspersistent activityregulator of g protein signalingretrosplenial cortexslow afterdepolarizationspatial navigationspatial orientation
Identifiers
PMID42157023
PMCPMC13580843
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