{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T18:05:36Z","timestamp":1789581936878,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1013752","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000}}],"reference-count":119,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Calcium dynamics controls learning and memory, and abnormal calcium dynamics have been implicated in neurodegenerative disorders, such as Alzheimer\u2019s disease (AD). Calcium dynamics are influenced by calcium-induced calcium release (CICR), which is mediated by ryanodine receptors (RyR) located on endoplasmic reticulum (ER) membrane. Calmodulin, one of the most abundant proteins in the brain, inhibits RyR2, expressed in the dendrites of hippocampal CA1 neurons, with several reported consequences: relief of this inhibition is responsible for heart failure, and enhancing calmodulin to RyR binding alleviates cell loss and AD-like neuronal hyperexcitability. To investigate the role of calmodulin in aging and AD, we built a sophisticated reaction-diffusion model of a dendritic branch with ER. We showed that relieving calmodulin inhibition of RyR2 increased spatial and temporal spread of calcium transients in the dendrite. This effect was also visible in a model of old age, where disinhibition of half of the RyR2 population increased spatial spread of calcium transients by a factor of 2, and disinhibition of RyR2 combined with increased concentration of calcium buffering molecules increased duration of calcium transients. Lower activation of plasma membrane calcium ATPase (PMCA), which is also activated by calmodulin and inhibited by\n                    <jats:inline-formula id=\"pcbi.1013752.e001\">\n                      <jats:alternatives>\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" id=\"pcbi.1013752.e001g\" mimetype=\"image\" position=\"anchor\" xlink:href=\"info:doi\/10.1371\/journal.pcbi.1013752.e001\" xlink:type=\"simple\"\/>\n                        <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" display=\"inline\" id=\"equation1\">\n                          <mml:mrow>\n                            <mml:mi>\u03b2<\/mml:mi>\n                          <\/mml:mrow>\n                        <\/mml:math>\n                      <\/jats:alternatives>\n                    <\/jats:inline-formula>\n                    -Amyloid oligomers, and not RyR2 disinhibition, led to an increase in resting intracellular calcium concentration as observed in AD. Overall, our research demonstrates that changes in calmodulin that are associated with AD and aging, by regulation of RyR2 (in old age) and PMCA (in AD), underlie changes in calcium dynamics that might have consequences for learning and memory.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1013752","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T17:42:28Z","timestamp":1789062148000},"page":"e1013752","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Calmodulin controls spatial and temporal specificity of calcium-induced calcium release"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2336-0848","authenticated-orcid":true,"given":"Joanna","family":"J\u0119drzejewska-Szmek","sequence":"first","affiliation":[{"name":"Nencki Institute of Experimental Biology Polish Academy of Sciences","place":["Warszawa, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim T.","family":"Blackwell","sequence":"additional","affiliation":[{"name":"University of Iowa","place":["Iowa City, Iowa, United States of America"],"department":["Roy J. Carver Department of Biomedical Engineering and Iowa Neuroscience Institute"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"pcbi.1013752.ref001","doi-asserted-by":"crossref","first-page":"437","DOI":"10.3389\/fnagi.2018.00437","article-title":"Executive Functions in Alzheimer Disease: A Systematic Review","volume":"10","author":"A Guarino","year":"2019","journal-title":"Front Aging Neurosci"},{"key":"pcbi.1013752.ref002","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1146\/annurev.neuro.28.061604.135703","article-title":"Dendritic computation","volume":"28","author":"M London","year":"2005","journal-title":"Annu Rev Neurosci"},{"issue":"45","key":"pcbi.1013752.ref003","doi-asserted-by":"crossref","first-page":"8460","DOI":"10.1523\/JNEUROSCI.1132-22.2022","article-title":"Dendritic Mechanisms for In Vivo Neural Computations and Behavior","volume":"42","author":"L Fischer","year":"2022","journal-title":"J Neurosci"},{"key":"pcbi.1013752.ref004","doi-asserted-by":"crossref","DOI":"10.3389\/fnmol.2019.00238","article-title":"Can NMDA spikes dictate computations of local networks and behavior?","volume":"12","author":"E Augusto","year":"2019","journal-title":"Front Mol Neurosci"},{"issue":"1","key":"pcbi.1013752.ref005","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.molmed.2023.10.008","article-title":"RyR-mediated calcium release in hippocampal health and disease","volume":"30","author":"C Hidalgo","year":"2024","journal-title":"Trends Mol Med"},{"issue":"1","key":"pcbi.1013752.ref006","doi-asserted-by":"crossref","first-page":"7289","DOI":"10.1038\/s41598-021-86822-x","article-title":"Enhancing calmodulin binding to ryanodine receptor is crucial to limit neuronal cell loss in Alzheimer disease","volume":"11","author":"Y Nakamura","year":"2021","journal-title":"Sci 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Shemer","year":"2008","journal-title":"PLoS Comput Biol"},{"issue":"5","key":"pcbi.1013752.ref010","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1083\/jcb.128.5.893","article-title":"The ryanodine receptor\/calcium channel genes are widely and differentially expressed in murine brain and peripheral tissues","volume":"128","author":"G Giannini","year":"1995","journal-title":"J Cell Biol"},{"issue":"1","key":"pcbi.1013752.ref011","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/s42003-022-03124-2","article-title":"Subcellular localization of hippocampal ryanodine receptor 2 and its role in neuronal excitability and memory","volume":"5","author":"F Hiess","year":"2022","journal-title":"Commun Biol"},{"key":"pcbi.1013752.ref012","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.bbrc.2022.10.024","article-title":"Hippocampal dendritic spines express the RyR3 but not the RyR2 ryanodine receptor isoform","volume":"633","author":"I Vega-V\u00e1squez","year":"2022","journal-title":"Biochem Biophys Res Commun"},{"issue":"3","key":"pcbi.1013752.ref013","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/nn.2746","article-title":"Calmodulin as a direct detector of Ca2+ signals","volume":"14","author":"GC Faas","year":"2011","journal-title":"Nat Neurosci"},{"issue":"4","key":"pcbi.1013752.ref014","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1093\/oxfordjournals.jbchem.a134019","article-title":"Quantitative determinations of calmodulin in the supernatant and particulate fractions of mammalian tissues","volume":"92","author":"S Kakiuchi","year":"1982","journal-title":"J Biochem"},{"issue":"6","key":"pcbi.1013752.ref015","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1111\/j.1471-4159.1977.tb12311.x","article-title":"Regional, cellular and subcellular distribution of calcium-activated cyclic nucleotide phosphodiesterase and calcium-dependent regulator in porcine brain","volume":"28","author":"JC Egrie","year":"1977","journal-title":"J Neurochem"},{"key":"pcbi.1013752.ref016","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.yjmcc.2015.06.009","article-title":"Oxidation of ryanodine receptor (RyR) and calmodulin enhance Ca release and pathologically alter, RyR structure and calmodulin affinity","volume":"85","author":"T Oda","year":"2015","journal-title":"J Mol Cell Cardiol"},{"issue":"12","key":"pcbi.1013752.ref017","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.3390\/cells9122655","article-title":"Ca2+ Dyshomeostasis Disrupts Neuronal and Synaptic Function in Alzheimer\u2019s Disease","volume":"9","author":"J McDaid","year":"2020","journal-title":"Cells"},{"issue":"1","key":"pcbi.1013752.ref018","doi-asserted-by":"crossref","first-page":"111943","DOI":"10.1016\/j.celrep.2022.111943","article-title":"Electrical signals in the ER are cell type and stimulus specific with extreme spatial compartmentalization in neurons","volume":"42","author":"EP Campbell","year":"2023","journal-title":"Cell Rep"},{"issue":"13","key":"pcbi.1013752.ref019","doi-asserted-by":"crossref","first-page":"3537","DOI":"10.1016\/j.celrep.2019.03.005","article-title":"Synapse-to-Nucleus Communication through NFAT Is Mediated by L-type Ca2+ Channel Ca2+ Spike Propagation to the Soma","volume":"26","author":"AR Wild","year":"2019","journal-title":"Cell Rep"},{"issue":"4","key":"pcbi.1013752.ref020","article-title":"Synapse-to-Nucleus ERK\u2192CREB Transcriptional Signaling Requires Dendrite-to-Soma Ca2+ Propagation Mediated by L-Type Voltage-Gated Ca2+ Channels","volume":"45","author":"KH Zent","year":"2025","journal-title":"J Neurosci"},{"issue":"33","key":"pcbi.1013752.ref021","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2102265118","article-title":"RyR-mediated Ca2+ release elicited by neuronal activity induces nuclear Ca2+ signals, CREB phosphorylation, and Npas4\/RyR2 expression","volume":"118","author":"P Lobos","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pcbi.1013752.ref022","doi-asserted-by":"crossref","first-page":"102399","DOI":"10.1016\/j.ceca.2021.102399","article-title":"Ryanodine receptor-mediated Ca2+ release and atlastin-2 GTPase activity contribute to IP3-induced dendritic Ca2+ signals in primary hippocampal neurons","volume":"96","author":"OA Ram\u00edrez","year":"2021","journal-title":"Cell Calcium"},{"issue":"1","key":"pcbi.1013752.ref023","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13408-018-0064-x","article-title":"What Is Required for Neuronal Calcium Waves? A Numerical Parameter Study","volume":"8","author":"M Breit","year":"2018","journal-title":"J Math Neurosci"},{"key":"pcbi.1013752.ref024","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1113\/jphysiol.2006.114231","article-title":"Modulation of calcium wave propagation in the dendrites and to the soma of rat hippocampal pyramidal neurons","volume":"575","author":"S Watanabe","year":"2006","journal-title":"J Physiol"},{"issue":"3","key":"pcbi.1013752.ref025","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S0896-6273(00)81125-3","article-title":"Synergistic release of Ca2+ from IP3-sensitive stores evoked by synaptic activation of mGluRs paired with backpropagating action potentials","volume":"24","author":"T Nakamura","year":"1999","journal-title":"Neuron"},{"issue":"2","key":"pcbi.1013752.ref026","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1093\/cercor\/bhm075","article-title":"MGluR-mediated calcium waves that invade the soma regulate firing in layer V medial prefrontal cortical pyramidal neurons","volume":"18","author":"AM Hagenston","year":"2008","journal-title":"Cereb Cortex"},{"issue":"4","key":"pcbi.1013752.ref027","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1002\/hipo.20644","article-title":"IP(3) mobilization and diffusion determine the timing window of Ca(2+) release by synaptic stimulation and a spike in rat CA1 pyramidal cells","volume":"20","author":"S Manita","year":"2010","journal-title":"Hippocampus"},{"issue":"7","key":"pcbi.1013752.ref028","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1113\/jphysiol.2012.245688","article-title":"Quantitative interactions between the A-type K+ current and inositol trisphosphate receptors regulate intraneuronal Ca2+ waves and synaptic plasticity","volume":"591","author":"S Ashhad","year":"2013","journal-title":"J Physiol"},{"issue":"4","key":"pcbi.1013752.ref029","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1162\/NECO_a_00712","article-title":"Neuronal calcium wave propagation varies with changes in endoplasmic reticulum parameters: a computer model","volume":"27","author":"SA Neymotin","year":"2015","journal-title":"Neural Comput"},{"issue":"6","key":"pcbi.1013752.ref030","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.1714409115","article-title":"Intracellular Ca2+ stores control in vivo neuronal hyperactivity in a mouse model of Alzheimer\u2019s disease","volume":"115","author":"C Lerdkrai","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"12","key":"pcbi.1013752.ref031","doi-asserted-by":"crossref","first-page":"3354","DOI":"10.1038\/s41418-020-0584-2","article-title":"Loss of Ryanodine Receptor 2 impairs neuronal activity-dependent remodeling of dendritic spines and triggers compensatory neuronal hyperexcitability","volume":"27","author":"F Bertan","year":"2020","journal-title":"Cell Death Differ"},{"issue":"7","key":"pcbi.1013752.ref032","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1005657","article-title":"\u03b2-adrenergic signaling broadly contributes to LTP induction","volume":"13","author":"J J\u0229drzejewska-Szmek","year":"2017","journal-title":"PLoS Comput Biol"},{"key":"pcbi.1013752.ref033","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.jtbi.2019.02.010","article-title":"Reaction-diffusion model for STIM-ORAI interaction: The role of ROS and mutations","volume":"470","author":"B Schmidt","year":"2019","journal-title":"J Theor Biol"},{"issue":"21","key":"pcbi.1013752.ref034","doi-asserted-by":"crossref","first-page":"7737","DOI":"10.1523\/JNEUROSCI.23-21-07737.2003","article-title":"Activity-evoked capacitative Ca2+ entry: implications in synaptic plasticity","volume":"23","author":"A Baba","year":"2003","journal-title":"J Neurosci"},{"issue":"2","key":"pcbi.1013752.ref035","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2024.11.029","article-title":"Periodic ER-plasma membrane junctions support long-range Ca2+ signal integration in dendrites","volume":"188","author":"L Benedetti","year":"2025","journal-title":"Cell"},{"issue":"2","key":"pcbi.1013752.ref036","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1529\/biophysj.105.075036","article-title":"Reaction diffusion modeling of calcium dynamics with realistic ER geometry","volume":"91","author":"S Means","year":"2006","journal-title":"Biophys J"},{"key":"pcbi.1013752.ref037","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S0301-4622(98)00125-2","article-title":"Spark-to-wave transition: saltatory transmission of calcium waves in cardiac myocytes","volume":"72","author":"J Keizer","year":"1998","journal-title":"Biophys Chem"},{"issue":"2","key":"pcbi.1013752.ref038","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/S0006-3495(04)74155-7","article-title":"Mechanism of calmodulin inhibition of cardiac sarcoplasmic reticulum Ca2+ release channel (ryanodine receptor)","volume":"86","author":"L Xu","year":"2004","journal-title":"Biophys J"},{"issue":"2","key":"pcbi.1013752.ref039","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1085\/jgp.201110706","article-title":"A mechanistic description of gating of the human cardiac ryanodine receptor in a regulated minimal environment","volume":"140","author":"S Mukherjee","year":"2012","journal-title":"J Gen Physiol"},{"issue":"5","key":"pcbi.1013752.ref040","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1054\/ceca.1999.0036","article-title":"Dynamic regulation of <> by plasma membrane Ca2 -ATPase and <> exchange during capacitative Ca2 entry in bovine vascular endothelial cells","volume":"25","author":"M Sedova","year":"1999","journal-title":"Cell Calcium"},{"issue":"4","key":"pcbi.1013752.ref041","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1016\/S0006-3495(99)77359-5","article-title":"Significance of Na\/Ca exchange for Ca2+ buffering and electrical activity in mouse pancreatic beta-cells","volume":"76","author":"D Gall","year":"1999","journal-title":"Biophys J"},{"issue":"3","key":"pcbi.1013752.ref042","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1073\/pnas.0605412104","article-title":"Differential distribution of NCX1 contributes to spine-dendrite compartmentalization in CA1 pyramidal cells","volume":"104","author":"A L\u00f6rincz","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pcbi.1013752.ref043","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1113\/jphysiol.2007.127860","article-title":"Spino-dendritic cross-talk in rodent Purkinje neurons mediated by endogenous Ca2+-binding proteins","volume":"581","author":"H Schmidt","year":"2007","journal-title":"J Physiol"},{"key":"pcbi.1013752.ref044","doi-asserted-by":"crossref","first-page":"48","DOI":"10.3389\/fncel.2015.00048","article-title":"Buffer mobility and the regulation of neuronal calcium domains","volume":"9","author":"EA Matthews","year":"2015","journal-title":"Front Cell Neurosci"},{"issue":"6","key":"pcbi.1013752.ref045","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1074\/jbc.272.6.3389","article-title":"Kinetic control of the dissociation pathway of calmodulin-peptide complexes","volume":"272","author":"SE Brown","year":"1997","journal-title":"J Biol Chem"},{"issue":"50","key":"pcbi.1013752.ref046","doi-asserted-by":"crossref","first-page":"49667","DOI":"10.1074\/jbc.C300372200","article-title":"A new role for IQ motif proteins in regulating calmodulin function","volume":"278","author":"JA Putkey","year":"2003","journal-title":"J Biol Chem"},{"issue":"11","key":"pcbi.1013752.ref047","doi-asserted-by":"crossref","first-page":"3848","DOI":"10.1529\/biophysj.107.106849","article-title":"Neurogranin controls the spatiotemporal pattern of postsynaptic Ca2+\/CaM signaling","volume":"93","author":"Y Kubota","year":"2007","journal-title":"Biophys J"},{"issue":"13","key":"pcbi.1013752.ref048","doi-asserted-by":"crossref","first-page":"3482","DOI":"10.1523\/JNEUROSCI.4171-05.2006","article-title":"Early and simultaneous emergence of multiple hippocampal biomarkers of aging is mediated by Ca2+-induced Ca2+ release","volume":"26","author":"JC Gant","year":"2006","journal-title":"J Neurosci"},{"issue":"1","key":"pcbi.1013752.ref049","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s13024-017-0169-9","article-title":"Soluble oligomeric amyloid-\u03b2 induces calcium dyshomeostasis that precedes synapse loss in the living mouse brain","volume":"12","author":"M Arbel-Ornath","year":"2017","journal-title":"Mol Neurodegener"},{"issue":"3","key":"pcbi.1013752.ref050","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1111\/j.1460-9568.2012.08159.x","article-title":"The development, distribution and density of the plasma membrane calcium ATPase 2 calcium pump in rat cochlear hair cells","volume":"36","author":"Q Chen","year":"2012","journal-title":"Eur J Neurosci"},{"issue":"8","key":"pcbi.1013752.ref051","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1085\/jgp.201812261","article-title":"Dendritic spine geometry and spine apparatus organization govern the spatiotemporal dynamics of calcium","volume":"151","author":"M Bell","year":"2019","journal-title":"J Gen Physiol"},{"issue":"3","key":"pcbi.1013752.ref052","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1523\/JNEUROSCI.3799-04.2005","article-title":"Endogenous Ca2+ buffer concentration and Ca2+ microdomains in hippocampal neurons","volume":"25","author":"A M\u00fcller","year":"2005","journal-title":"J Neurosci"},{"issue":"2","key":"pcbi.1013752.ref053","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1006\/abbi.1993.1463","article-title":"Characterization of a 7.5-kDa protein kinase C substrate (RC3 protein, neurogranin) from rat brain","volume":"305","author":"KP Huang","year":"1993","journal-title":"Arch Biochem Biophys"},{"issue":"2","key":"pcbi.1013752.ref054","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S0143-4160(98)90076-8","article-title":"Functional measurements of [Ca2+] in the endoplasmic reticulum using a herpes virus to deliver targeted aequorin","volume":"24","author":"MT Alonso","year":"1998","journal-title":"Cell Calcium"},{"issue":"5089","key":"pcbi.1013752.ref055","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1126\/science.1465619","article-title":"Range of messenger action of calcium ion and inositol 1,4,5-trisphosphate","volume":"258","author":"NL Allbritton","year":"1992","journal-title":"Science"},{"issue":"8","key":"pcbi.1013752.ref056","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1016\/j.bbamcr.2016.04.021","article-title":"Tracking and localization of calmodulin in live cells","volume":"1863","author":"CK Johnson","year":"2016","journal-title":"Biochim Biophys Acta"},{"issue":"16","key":"pcbi.1013752.ref057","doi-asserted-by":"crossref","first-page":"5850","DOI":"10.1073\/pnas.0407855102","article-title":"Calbindin D28k targets myo-inositol monophosphatase in spines and dendrites of cerebellar Purkinje neurons","volume":"102","author":"H Schmidt","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pcbi.1013752.ref058","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0006-3495(00)76281-3","article-title":"An image-based model of calcium waves in differentiated neuroblastoma cells","volume":"79","author":"CC Fink","year":"2000","journal-title":"Biophys J"},{"key":"pcbi.1013752.ref059","unstructured":"Berg JM, Tymoczko JL, Stryer L. Biochemistry, Fifth Edition. No. pts. 1-34 in [NCBI bookshelf]. W. H. Freeman. 2002. Available from: https:\/\/books.google.pl\/books?id=jQKGAAAACAAJ"},{"issue":"32","key":"pcbi.1013752.ref060","doi-asserted-by":"crossref","first-page":"21458","DOI":"10.1016\/S0021-9258(18)54661-5","article-title":"Expression of calreticulin in Escherichia coli and identification of its Ca2+ binding domains","volume":"266","author":"S Baksh","year":"1991","journal-title":"J Biol Chem"},{"issue":"1","key":"pcbi.1013752.ref061","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0006-3495(02)75149-7","article-title":"Termination of cardiac Ca(2+) sparks: an investigative mathematical model of calcium-induced calcium release","volume":"83","author":"EA Sobie","year":"2002","journal-title":"Biophys J"},{"issue":"2","key":"pcbi.1013752.ref062","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1038\/cr.2010.131","article-title":"Graded activation of CRAC channel by binding of different numbers of STIM1 to Orai1 subunits","volume":"21","author":"Z Li","year":"2011","journal-title":"Cell Res"},{"key":"pcbi.1013752.ref063","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3389\/fnsyn.2015.00017","article-title":"Computational reconstitution of spine calcium transients from individual proteins","volume":"7","author":"TM Bartol","year":"2015","journal-title":"Front Synaptic Neurosci"},{"key":"pcbi.1013752.ref064","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jchemneu.2017.11.008","article-title":"Cellular calcium signaling in the aging brain","volume":"95","author":"R Chandran","year":"2019","journal-title":"J Chem Neuroanat"},{"issue":"2","key":"pcbi.1013752.ref065","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1021\/tx990142a","article-title":"The sensitivity of carboxyl-terminal methionines in calmodulin isoforms to oxidation by H(2)O(2) modulates the ability to activate the plasma membrane Ca-ATPase","volume":"13","author":"D Yin","year":"2000","journal-title":"Chem Res Toxicol"},{"issue":"23","key":"pcbi.1013752.ref066","doi-asserted-by":"crossref","first-page":"20144","DOI":"10.1074\/jbc.M010771200","article-title":"Calmodulin binding and inhibition of cardiac muscle calcium release channel (ryanodine receptor)","volume":"276","author":"DM Balshaw","year":"2001","journal-title":"J Biol Chem"},{"issue":"5","key":"pcbi.1013752.ref067","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1111\/j.1471-4159.2012.07918.x","article-title":"Decreases in plasma membrane Ca2+-ATPase in brain synaptic membrane rafts from aged rats","volume":"123","author":"L Jiang","year":"2012","journal-title":"J Neurochem"},{"issue":"5","key":"pcbi.1013752.ref068","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/S0197-4580(98)00078-5","article-title":"Age-related decrease in brain synaptic membrane Ca2 -ATPase in F344\/BNF1 rats","volume":"19","author":"A Zaidi","year":"1998","journal-title":"Neurobiol 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Cortex"},{"issue":"5","key":"pcbi.1013752.ref075","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.3390\/ijms26052101","article-title":"Aging Favors Calcium Activation of Ryanodine Receptor Channels from Brain Cortices and Hippocampi and Hinders Learning and Memory in Male Rats","volume":"26","author":"J More","year":"2025","journal-title":"Int J Mol Sci"},{"key":"pcbi.1013752.ref076","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.neuint.2007.10.002","article-title":"Calcium dysregulation in Alzheimer\u2019s disease","volume":"52","author":"L Bojarski","year":"2008","journal-title":"Neurochem Int"},{"issue":"1","key":"pcbi.1013752.ref077","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1111\/j.1471-4159.2007.05135.x","article-title":"Increased intraneuronal resting [Ca2+] in adult Alzheimer\u2019s disease mice","volume":"105","author":"JR Lopez","year":"2008","journal-title":"J Neurochem"},{"issue":"2","key":"pcbi.1013752.ref078","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.neuron.2008.06.008","article-title":"Abeta plaques lead to aberrant regulation of calcium homeostasis in vivo resulting in structural and functional disruption of neuronal networks","volume":"59","author":"KV Kuchibhotla","year":"2008","journal-title":"Neuron"},{"issue":"24","key":"pcbi.1013752.ref079","doi-asserted-by":"crossref","first-page":"18195","DOI":"10.1074\/jbc.M000040200","article-title":"Presenilin-1 mutations increase levels of ryanodine receptors and calcium release in PC12 cells and cortical neurons","volume":"275","author":"SL Chan","year":"2000","journal-title":"J Biol Chem"},{"issue":"30","key":"pcbi.1013752.ref080","doi-asserted-by":"crossref","first-page":"9458","DOI":"10.1523\/JNEUROSCI.2047-09.2009","article-title":"Deviant ryanodine receptor-mediated calcium release resets synaptic homeostasis in presymptomatic 3xTg-AD 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Sabatini","year":"2002","journal-title":"Neuron"},{"issue":"5","key":"pcbi.1013752.ref084","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1523\/JNEUROSCI.20-05-01722.2000","article-title":"Mechanisms of calcium decay kinetics in hippocampal spines: role of spine calcium pumps and calcium diffusion through the spine neck in biochemical compartmentalization","volume":"20","author":"A Majewska","year":"2000","journal-title":"J Neurosci"},{"issue":"12","key":"pcbi.1013752.ref085","doi-asserted-by":"crossref","first-page":"125104","DOI":"10.1063\/1.4944575","article-title":"Asynchronous \u03c4-leaping","volume":"144","author":"Z J\u0119drzejewski-Szmek","year":"2016","journal-title":"J Chem Phys"},{"key":"pcbi.1013752.ref086","doi-asserted-by":"crossref","unstructured":"Seabold S, Perktold J. statsmodels: Econometric and statistical modeling with python. In: 9th Python in Science Conference. 2010.","DOI":"10.25080\/Majora-92bf1922-011"},{"issue":"10","key":"pcbi.1013752.ref087","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1002182","article-title":"Barriers to diffusion in dendrites and estimation of calcium spread following synaptic inputs","volume":"7","author":"A Biess","year":"2011","journal-title":"PLoS Comput Biol"},{"issue":"4678","key":"pcbi.1013752.ref088","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1126\/science.6494926","article-title":"Prolonged Ca2+-dependent afterhyperpolarizations in hippocampal neurons of aged rats","volume":"226","author":"PW Landfield","year":"1984","journal-title":"Science"},{"issue":"19","key":"pcbi.1013752.ref089","doi-asserted-by":"crossref","first-page":"6286","DOI":"10.1523\/JNEUROSCI.16-19-06286.1996","article-title":"Aging changes in voltage-gated calcium currents in hippocampal CA1 neurons","volume":"16","author":"LW Campbell","year":"1996","journal-title":"J Neurosci"},{"issue":"24","key":"pcbi.1013752.ref090","doi-asserted-by":"crossref","first-page":"9744","DOI":"10.1523\/JNEUROSCI.21-24-09744.2001","article-title":"Elevated postsynaptic [Ca2+]i and L-type calcium channel activity in aged hippocampal neurons: relationship to impaired synaptic plasticity","volume":"21","author":"O Thibault","year":"2001","journal-title":"J Neurosci"},{"issue":"2","key":"pcbi.1013752.ref091","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.neuroscience.2005.05.044","article-title":"Caloric restriction prevents aging-associated changes in spike-mediated Ca2+ accumulation and the slow afterhyperpolarization in hippocampal CA1 pyramidal neurons","volume":"135","author":"P Hemond","year":"2005","journal-title":"Neuroscience"},{"issue":"5","key":"pcbi.1013752.ref092","doi-asserted-by":"crossref","first-page":"2586","DOI":"10.1152\/jn.00577.2010","article-title":"Redox sensitive calcium stores underlie enhanced after hyperpolarization of aged neurons: role for ryanodine receptor mediated calcium signaling","volume":"104","author":"K Bodhinathan","year":"2010","journal-title":"J Neurophysiol"},{"key":"pcbi.1013752.ref093","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3389\/fnagi.2017.00111","article-title":"Aging Impairs Hippocampal- Dependent Recognition Memory and LTP and Prevents the Associated RyR Up-regulation","volume":"9","author":"A Arias-Cavieres","year":"2017","journal-title":"Front Aging Neurosci"},{"issue":"19","key":"pcbi.1013752.ref094","doi-asserted-by":"crossref","first-page":"5180","DOI":"10.1523\/JNEUROSCI.0739-06.2006","article-title":"Enhanced ryanodine receptor recruitment contributes to Ca2+ disruptions in young, adult, and aged Alzheimer\u2019s disease mice","volume":"26","author":"GE Stutzmann","year":"2006","journal-title":"J Neurosci"},{"issue":"6","key":"pcbi.1013752.ref095","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1096\/fj.08-121459","article-title":"Altered Ca2 dependence of synaptosomal plasma membrane Ca2 -ATPase in human brain affected by Alzheimer\u2019s disease","volume":"23","author":"M Berrocal","year":"2009","journal-title":"FASEB J"},{"issue":"7","key":"pcbi.1013752.ref096","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1016\/j.bbadis.2015.04.007","article-title":"Inhibition of PMCA activity by tau as a function of aging and Alzheimer\u2019s neuropathology","volume":"1852","author":"M Berrocal","year":"2015","journal-title":"Biochim Biophys Acta"},{"issue":"6","key":"pcbi.1013752.ref097","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1016\/j.bbamcr.2016.10.023","article-title":"Phospholipids and calmodulin modulate the inhibition of PMCA activity by tau","volume":"1864","author":"M Berrocal","year":"2017","journal-title":"Biochim Biophys Acta Mol Cell Res"},{"issue":"6","key":"pcbi.1013752.ref098","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/j.bbadis.2012.02.013","article-title":"Calmodulin antagonizes amyloid-\u03b2 peptides-mediated inhibition of brain plasma membrane Ca(2+)-ATPase","volume":"1822","author":"M Berrocal","year":"2012","journal-title":"Biochim Biophys Acta"},{"issue":"35","key":"pcbi.1013752.ref099","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2407324121","article-title":"L-type Ca2+ channel activation of STIM1-Orai1 signaling remodels the dendritic spine ER to maintain long-term structural plasticity","volume":"121","author":"PJ Dittmer","year":"2024","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6355","key":"pcbi.1013752.ref100","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1126\/science.aan3846","article-title":"Behavioral time scale synaptic plasticity underlies CA1 place fields","volume":"357","author":"KC Bittner","year":"2017","journal-title":"Science"},{"issue":"6586","key":"pcbi.1013752.ref101","doi-asserted-by":"crossref","DOI":"10.1126\/science.abm1670","article-title":"Compartment-specific tuning of dendritic feature selectivity by intracellular Ca2+ release","volume":"375","author":"JK O\u2019Hare","year":"2022","journal-title":"Science"},{"issue":"1","key":"pcbi.1013752.ref102","doi-asserted-by":"crossref","first-page":"15624","DOI":"10.1038\/s41598-018-33343-9","article-title":"Spine-to-Dendrite Calcium Modeling Discloses Relevance for Precise Positioning of Ryanodine Receptor-Containing Spine Endoplasmic Reticulum","volume":"8","author":"M Breit","year":"2018","journal-title":"Sci Rep"},{"issue":"6","key":"pcbi.1013752.ref103","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.2006202","article-title":"Fast calcium transients in dendritic spines driven by extreme statistics","volume":"17","author":"K Basnayake","year":"2019","journal-title":"PLoS Biol"},{"key":"pcbi.1013752.ref104","doi-asserted-by":"crossref","first-page":"102804","DOI":"10.1016\/j.conb.2023.102804","article-title":"Making time and space for calcium control of neuron activity","volume":"83","author":"J J\u0119drzejewska-Szmek","year":"2023","journal-title":"Curr Opin Neurobiol"},{"issue":"11","key":"pcbi.1013752.ref105","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1016\/j.bpj.2021.03.027","article-title":"Stochastic reaction-diffusion modeling of calcium dynamics in 3D dendritic spines of Purkinje cells","volume":"120","author":"VN Friedhoff","year":"2021","journal-title":"Biophys J"},{"issue":"6","key":"pcbi.1013752.ref106","doi-asserted-by":"crossref","first-page":"3477","DOI":"10.1016\/S0006-3495(96)79543-7","article-title":"Ryanodine receptor adaptation and Ca2+(-)induced Ca2+ release-dependent Ca2+ oscillations","volume":"71","author":"J Keizer","year":"1996","journal-title":"Biophys J"},{"key":"pcbi.1013752.ref107","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.cell.2011.11.056","article-title":"Local zones of endoplasmic reticulum complexity confine cargo in neuronal dendrites","volume":"148","author":"T Wang","year":"2012","journal-title":"Cell"},{"issue":"1","key":"pcbi.1013752.ref108","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/s41467-017-02751-2","article-title":"Hotspots of dendritic spine turnover facilitate clustered spine addition and learning and memory","volume":"9","author":"AC Frank","year":"2018","journal-title":"Nat Commun"},{"issue":"2","key":"pcbi.1013752.ref109","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0014-2999(02)01843-5","article-title":"Sustained Ca2 -induced Ca2 -release underlies the post-glutamate lethal Ca2 plateau in older cultured hippocampal neurons","volume":"447","author":"GV Clodfelter","year":"2002","journal-title":"Eur J Pharmacol"},{"issue":"41","key":"pcbi.1013752.ref110","doi-asserted-by":"crossref","first-page":"12001","DOI":"10.1021\/bi034565u","article-title":"Oxidative inactivation of purified plasma membrane Ca2 -ATPase by hydrogen peroxide and protection by calmodulin","volume":"42","author":"A Zaidi","year":"2003","journal-title":"Biochemistry"},{"issue":"24","key":"pcbi.1013752.ref111","doi-asserted-by":"crossref","first-page":"7833","DOI":"10.1523\/JNEUROSCI.0573-09.2009","article-title":"Synaptic activation and membrane potential changes modulate the frequency of spontaneous elementary Ca2+ release events in the dendrites of pyramidal neurons","volume":"29","author":"S Manita","year":"2009","journal-title":"J Neurosci"},{"issue":"6","key":"pcbi.1013752.ref112","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.ceca.2012.08.001","article-title":"Developmental profile of localized spontaneous Ca(2+) release events in the dendrites of rat hippocampal pyramidal neurons","volume":"52","author":"K Miyazaki","year":"2012","journal-title":"Cell Calcium"},{"issue":"45","key":"pcbi.1013752.ref113","doi-asserted-by":"crossref","first-page":"17777","DOI":"10.1523\/JNEUROSCI.2735-13.2013","article-title":"Ca2+ sparks and puffs are generated and interact in rat hippocampal CA1 pyramidal neuron dendrites","volume":"33","author":"K Miyazaki","year":"2013","journal-title":"J Neurosci"},{"issue":"11","key":"pcbi.1013752.ref114","doi-asserted-by":"crossref","first-page":"3864","DOI":"10.1523\/JNEUROSCI.2253-13.2014","article-title":"Dendritic calcium nonlinearities switch the direction of synaptic plasticity in fast-spiking interneurons","volume":"34","author":"O Camir\u00e9","year":"2014","journal-title":"J Neurosci"},{"issue":"3","key":"pcbi.1013752.ref115","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0018250","article-title":"Calcium ions promote formation of amyloid \u03b2-peptide (1-40) oligomers causally implicated in neuronal toxicity of Alzheimer\u2019s disease","volume":"6","author":"A Itkin","year":"2011","journal-title":"PLoS One"},{"issue":"3","key":"pcbi.1013752.ref116","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.0959-9673.2005.00427.x","article-title":"Mitochondrial dysfunction and Alzheimer\u2019s disease: role of amyloid-beta peptide alcohol dehydrogenase (ABAD)","volume":"86","author":"SD Yan","year":"2005","journal-title":"Int J Exp Pathol"},{"issue":"1","key":"pcbi.1013752.ref117","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1006\/exnr.1997.6750","article-title":"Increased peroxidation and reduced antioxidant enzyme activity in Alzheimer\u2019s disease","volume":"150","author":"DL Marcus","year":"1998","journal-title":"Exp Neurol"},{"issue":"6","key":"pcbi.1013752.ref118","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1002\/jnr.20135","article-title":"Involvement of endoplasmic reticulum Ca2+ release through ryanodine and inositol 1,4,5-triphosphate receptors in the neurotoxic effects induced by the amyloid-beta peptide","volume":"76","author":"E Ferreiro","year":"2004","journal-title":"J Neurosci Res"},{"issue":"7","key":"pcbi.1013752.ref119","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1089\/ars.2010.3287","article-title":"Amyloid \u03b2-peptide oligomers stimulate RyR-mediated Ca2+ release inducing mitochondrial fragmentation in hippocampal neurons and prevent RyR-mediated dendritic spine remodeling produced by BDNF","volume":"14","author":"AC Paula-Lima","year":"2011","journal-title":"Antioxid Redox Signal"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1013752","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000}}],"container-title":["PLOS Computational 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