{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T11:55:04Z","timestamp":1768478104547,"version":"3.49.0"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1012259","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T00:00:00Z","timestamp":1721174400000}}],"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:00:00Z","timestamp":1720137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","award":["101017716"],"award-info":[{"award-number":["101017716"]}],"id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PID2021-127311NB-I00"],"award-info":[{"award-number":["PID2021-127311NB-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["MICIN\/AEI\/10.13039\/501100011033\/FEDER"],"award-info":[{"award-number":["MICIN\/AEI\/10.13039\/501100011033\/FEDER"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","award":["101017716"],"award-info":[{"award-number":["101017716"]}],"id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["CEX2018-000792-M"],"award-info":[{"award-number":["CEX2018-000792-M"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ICREA Academia program"},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["RFIS-I grant 32350410413"],"award-info":[{"award-number":["RFIS-I grant 32350410413"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["CPP2022-009659"],"award-info":[{"award-number":["CPP2022-009659"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["RTC2019-007329-1"],"award-info":[{"award-number":["RTC2019-007329-1"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["PID2022-141900OB-I00"],"award-info":[{"award-number":["PID2022-141900OB-I00"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008666","name":"Fundaci\u00f3 la Marat\u00f3 de TV3","doi-asserted-by":"publisher","award":["202212-30-31-32"],"award-info":[{"award-number":["202212-30-31-32"]}],"id":[{"id":"10.13039\/100008666","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","award":["H2020-899986"],"award-info":[{"award-number":["H2020-899986"]}],"id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","award":["GO-DS21-848077"],"award-info":[{"award-number":["GO-DS21-848077"]}],"id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Cognitive disorders, including Down syndrome (DS), present significant morphological alterations in neuron architectural complexity. However, the relationship between neuromorphological alterations and impaired brain function is not fully understood. To address this gap, we propose a novel computational model that accounts for the observed cell deformations in DS. The model consists of a cross-sectional layer of the mouse motor cortex, composed of 3000 neurons. The network connectivity is obtained by accounting explicitly for two single-neuron morphological parameters: the mean dendritic tree radius and the spine density in excitatory pyramidal cells. We obtained these values by fitting reconstructed neuron data corresponding to three mouse models: wild-type (WT), transgenic (TgDyrk1A), and trisomic (Ts65Dn). Our findings reveal a dynamic interplay between pyramidal and fast-spiking interneurons leading to the emergence of gamma activity (\u223c40 Hz). In the DS models this gamma activity is diminished, corroborating experimental observations and validating our computational methodology. We further explore the impact of disrupted excitation-inhibition balance by mimicking the reduction recurrent inhibition present in DS. In this case, gamma power exhibits variable responses as a function of the external input to the network. Finally, we perform a numerical exploration of the morphological parameter space, unveiling the direct influence of each structural parameter on gamma frequency and power. Our research demonstrates a clear link between changes in morphology and the disruption of gamma oscillations in DS. This work underscores the potential of computational modeling to elucidate the relationship between neuron architecture and brain function, and ultimately improve our understanding of cognitive disorders.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1012259","type":"journal-article","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T17:46:41Z","timestamp":1720201601000},"page":"e1012259","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Modeling the impact of neuromorphological alterations in Down syndrome on fast neural oscillations"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2010-7924","authenticated-orcid":true,"given":"Pau","family":"Clusella","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2036-2204","authenticated-orcid":true,"given":"Linus","family":"Manubens-Gil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3716-7520","authenticated-orcid":true,"given":"Jordi","family":"Garcia-Ojalvo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0853-6865","authenticated-orcid":true,"given":"Mara","family":"Dierssen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,7,5]]},"reference":[{"issue":"6","key":"pcbi.1012259.ref001","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/S1474-4422(10)70112-5","article-title":"Cognitive Deficits and Associated Neurological Complications in Individuals with Down\u2019s Syndrome","volume":"9","author":"IT Lott","year":"2010","journal-title":"The Lancet Neurology"},{"issue":"7","key":"pcbi.1012259.ref002","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1093\/cercor\/13.7.758","article-title":"Alterations of Neocortical Pyramidal Cell Phenotype in the Ts65Dn Mouse Model of Down Syndrome: Effects of Environmental Enrichment","volume":"13","author":"M Dierssen","year":"2003","journal-title":"Cerebral Cortex"},{"issue":"12","key":"pcbi.1012259.ref003","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1093\/cercor\/bhr362","article-title":"Dyrk1A Influences Neuronal Morphogenesis Through Regulation of Cytoskeletal Dynamics in Mammalian Cortical Neurons","volume":"22","author":"M Martinez de Lagran","year":"2012","journal-title":"Cerebral Cortex"},{"key":"pcbi.1012259.ref004","article-title":"The lncRNA Snhg11, a New Candidate Contributing to Neurogenesis, Plasticity and Memory Deficits in Down Syndrome","author":"M Dierssen","year":"2023","journal-title":"Review"},{"issue":"1","key":"pcbi.1012259.ref005","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1002\/cne.901670105","article-title":"Pyramidal Cell Abnormalities in the Motor Cortex of a Child with Down\u2019s Syndrome. A Golgi Study","volume":"167","author":"M Marin-Padilla","year":"1976","journal-title":"Journal of Comparative Neurology"},{"key":"pcbi.1012259.ref006","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3389\/fnsys.2019.00017","article-title":"Outer Brain Oscillations in Down Syndrome","volume":"13","author":"M Ruiz-Mejias","year":"2019","journal-title":"Frontiers in Systems Neuroscience"},{"issue":"13","key":"pcbi.1012259.ref007","doi-asserted-by":"crossref","first-page":"3648","DOI":"10.1523\/JNEUROSCI.2517-15.2016","article-title":"Overexpression of Dyrk1A, a Down Syndrome Candidate, Decreases Excitability and Impairs Gamma Oscillations in the Prefrontal Cortex","volume":"36","author":"M Ruiz-Mejias","year":"2016","journal-title":"The Journal of Neuroscience"},{"issue":"3","key":"pcbi.1012259.ref008","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.cell.2012.02.046","article-title":"Inhibitory Interneuron Deficit Links Altered Network Activity and Cognitive Dysfunction in Alzheimer Model","volume":"149","author":"L Verret","year":"2012","journal-title":"Cell"},{"key":"pcbi.1012259.ref009","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.conb.2018.07.009","article-title":"Gamma oscillations in cognitive disorders","volume":"52","author":"AJ Mably","year":"2018","journal-title":"Current opinion in neurobiology"},{"issue":"12","key":"pcbi.1012259.ref010","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.tics.2003.10.012","article-title":"Synchronous neural oscillations and cognitive processes","volume":"7","author":"LM Ward","year":"2003","journal-title":"Trends in cognitive sciences"},{"key":"pcbi.1012259.ref011","doi-asserted-by":"crossref","DOI":"10.1093\/acprof:oso\/9780195301069.001.0001","volume-title":"Rhythms of the Brain","author":"G Buzs\u00e1ki","year":"2006"},{"issue":"1","key":"pcbi.1012259.ref012","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.neuron.2016.12.003","article-title":"Perceptual decision making in rodents, monkeys, and humans","volume":"93","author":"TD Hanks","year":"2017","journal-title":"Neuron"},{"issue":"1","key":"pcbi.1012259.ref013","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1002\/dneu.20814","article-title":"Multiple Origins of the Cortical Gamma Rhythm","volume":"71","author":"MA Whittington","year":"2011","journal-title":"Developmental Neurobiology"},{"issue":"1","key":"pcbi.1012259.ref014","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1146\/annurev-neuro-062111-150444","article-title":"Mechanisms of Gamma Oscillations","volume":"35","author":"G Buzs\u00e1ki","year":"2012","journal-title":"Annual Review of Neuroscience"},{"issue":"2","key":"pcbi.1012259.ref015","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ijpsycho.2013.07.005","article-title":"A Review of Gamma Oscillations in Healthy Subjects and in Cognitive Impairment","volume":"90","author":"E Ba\u015far","year":"2013","journal-title":"International Journal of Psychophysiology"},{"issue":"26","key":"pcbi.1012259.ref016","doi-asserted-by":"crossref","first-page":"10720","DOI":"10.1073\/pnas.1102017108","article-title":"Adaptation-Induced Synchronization in Laminar Cortical Circuits","volume":"108","author":"BJ Hansen","year":"2011","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"9","key":"pcbi.1012259.ref017","doi-asserted-by":"crossref","first-page":"3626","DOI":"10.1073\/pnas.1309714111","article-title":"Stimulus Repetition Modulates Gamma-Band Synchronization in Primate Visual Cortex","volume":"111","author":"NM Brunet","year":"2014","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"pcbi.1012259.ref018","first-page":"263","volume-title":"Molecular genetics of chromosome 21 and Down syndrome","author":"Muriel T Davisson","year":"1990"},{"issue":"18","key":"pcbi.1012259.ref019","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1093\/hmg\/10.18.1915","article-title":"Neurodevelopmental delay, motor abnormalities and cognitive deficits in transgenic mice overexpressing Dyrk1A (minibrain), a murine model of Down\u2019s syndrome","volume":"10","author":"X Altafaj","year":"2001","journal-title":"Human Molecular Genetics"},{"issue":"1","key":"pcbi.1012259.ref020","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.nbd.2003.10.002","article-title":"Motor phenotypic alterations in TgDyrk1a transgenic mice implicate DYRK1A in Down syndrome motor dysfunction","volume":"15","author":"M Mart\u00ednez de Lagr\u00e1n","year":"2004","journal-title":"Neurobiology of Disease"},{"issue":"6","key":"pcbi.1012259.ref021","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1109\/TNN.2003.820440","article-title":"Simple model of spiking neurons","volume":"14","author":"EM Izhikevich","year":"2003","journal-title":"IEEE Transactions on Neural Networks"},{"issue":"9","key":"pcbi.1012259.ref022","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/nphys2686","article-title":"Noise focusing and the emergence of coherent activity in neuronal cultures","volume":"9","author":"JG Orlandi","year":"2013","journal-title":"Nature Physics"},{"issue":"1","key":"pcbi.1012259.ref023","doi-asserted-by":"crossref","first-page":"13864","DOI":"10.1038\/s41598-022-18024-y","article-title":"A Realistic Morpho-Anatomical Connection Strategy for Modelling Full-Scale Point-Neuron Microcircuits","volume":"12","author":"D Gandolfi","year":"2022","journal-title":"Scientific Reports"},{"issue":"4","key":"pcbi.1012259.ref024","first-page":"387","article-title":"Dendritic Organization in the Neurons of the Visual and Motor Cortices of the Cat","volume":"87","author":"DA Sholl","year":"1953","journal-title":"Journal of Anatomy"},{"issue":"3","key":"pcbi.1012259.ref025","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1023\/A:1008925309027","article-title":"Dynamics of Sparsely Connected Networks of Excitatory and Inhibitory Spiking Neurons","volume":"8","author":"N Brunel","year":"2000","journal-title":"Journal of Computational Neuroscience"},{"issue":"1","key":"pcbi.1012259.ref026","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1152\/jn.01095.2002","article-title":"What Determines the Frequency of Fast Network Oscillations With Irregular Neural Discharges? I. Synaptic Dynamics and Excitation-Inhibition Balance","volume":"90","author":"N Brunel","year":"2003","journal-title":"Journal of Neurophysiology"},{"issue":"3","key":"pcbi.1012259.ref027","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1152\/physrev.00035.2008","article-title":"Neurophysiological and Computational Principles of Cortical Rhythms in Cognition","volume":"90","author":"XJ Wang","year":"2010","journal-title":"Physiological Reviews"},{"issue":"1","key":"pcbi.1012259.ref028","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/nrn2044","article-title":"Synaptic Mechanisms of Synchronized Gamma Oscillations in Inhibitory Interneuron Networks","volume":"8","author":"M Bartos","year":"2007","journal-title":"Nature Reviews Neuroscience"},{"issue":"19","key":"pcbi.1012259.ref029","doi-asserted-by":"crossref","first-page":"7002","DOI":"10.1073\/pnas.0502366102","article-title":"Background Gamma Rhythmicity and Attention in Cortical Local Circuits: A Computational Study","volume":"102","author":"C B\u00f6rgers","year":"2005","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"pcbi.1012259.ref030","article-title":"Distinguishing Mechanisms of Gamma Frequency Oscillations in Human Current Source Signals Using a Computational Model of a Laminar Neocortical Network","volume":"7","author":"S Lee","year":"2013","journal-title":"Frontiers in Human Neuroscience"},{"key":"pcbi.1012259.ref031","doi-asserted-by":"crossref","DOI":"10.3389\/fncom.2015.00120","article-title":"An Algorithm to Predict the Connectome of Neural Microcircuits","volume":"9","author":"MW Reimann","year":"2015","journal-title":"Frontiers in Computational Neuroscience"},{"issue":"2","key":"pcbi.1012259.ref032","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.cell.2015.09.029","article-title":"Reconstruction and Simulation of Neocortical Microcircuitry","volume":"163","author":"H Markram","year":"2015","journal-title":"Cell"},{"issue":"2","key":"pcbi.1012259.ref033","doi-asserted-by":"crossref","first-page":"110677","DOI":"10.1016\/j.celrep.2022.110677","article-title":"The Impact of Neuron Morphology on Cortical Network Architecture","volume":"39","author":"D Udvary","year":"2022","journal-title":"Cell Reports"},{"issue":"17","key":"pcbi.1012259.ref034","doi-asserted-by":"crossref","first-page":"9554","DOI":"10.1073\/pnas.2000671117","article-title":"The Microcircuits of Striatum in Silico","volume":"117","author":"JJJ Hjorth","year":"2020","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"pcbi.1012259.ref035","doi-asserted-by":"crossref","DOI":"10.3389\/fnana.2014.00091","article-title":"Parametric Anatomical Modeling: A Method for Modeling the Anatomical Layout of Neurons and Their Projections","volume":"8","author":"M Pyka","year":"2014","journal-title":"Frontiers in Neuroanatomy"},{"key":"pcbi.1012259.ref036","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3389\/fninf.2019.00037","article-title":"Reconstruction and Simulation of a Scaffold Model of the Cerebellar Network","volume":"13","author":"S Casali","year":"2019","journal-title":"Frontiers in Neuroinformatics"},{"issue":"6515","key":"pcbi.1012259.ref037","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1038\/373612a0","article-title":"Synchronized oscillations in interneuron networks driven by metabotropic glutamate receptor activation","volume":"373","author":"MA Whittington","year":"1995","journal-title":"Nature"},{"issue":"7","key":"pcbi.1012259.ref038","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1162\/089976699300016179","article-title":"Fast Global Oscillations in Networks of Integrate-and-Fire Neurons with Low Firing Rates","volume":"11","author":"N Brunel","year":"1999","journal-title":"Neural Computation"},{"issue":"3","key":"pcbi.1012259.ref039","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/S0167-8760(00)00173-2","article-title":"Inhibition-based rhythms: experimental and mathematical observations on network dynamics","volume":"38","author":"MA Whittington","year":"2000","journal-title":"International Journal of Psychophysiology"},{"issue":"2","key":"pcbi.1012259.ref040","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1007\/BF00687074","article-title":"Intracellular Lucifer Yellow Staining and Electron Microscopy of Neurones in Slices of Fixed Epitumourous Human Cortical Tissue","volume":"75","author":"EH Buhl","year":"1987","journal-title":"Acta Neuropathologica"},{"issue":"2","key":"pcbi.1012259.ref041","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/0165-0270(88)90157-4","article-title":"Intracellular Injection of Lucifer Yellow into Cortical Neurons in Lightly Fixed Sections and Its Application to Human Autopsy Material","volume":"26","author":"G Einstein","year":"1988","journal-title":"Journal of Neuroscience Methods"},{"issue":"5","key":"pcbi.1012259.ref042","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1093\/cercor\/7.5.422","article-title":"Neuronal Composition and Morphology in Layer IV of Two Vibrissal Barrel Subfields of Rat Cortex","volume":"7","author":"GN Elston","year":"1997","journal-title":"Cerebral Cortex"},{"issue":"3","key":"pcbi.1012259.ref043","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.pneurobio.2010.05.001","article-title":"A Modeler\u2019s View on the Spatial Structure of Intrinsic Horizontal Connectivity in the Neocortex","volume":"92","author":"N Voges","year":"2010","journal-title":"Progress in Neurobiology"},{"key":"pcbi.1012259.ref044","article-title":"GNU Scientific Library: Reference Manual","author":"M Galassi","year":"2003","journal-title":"Network Theory"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1012259","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T00:00:00Z","timestamp":1721174400000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1012259","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T17:37:45Z","timestamp":1721237865000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1012259"}},"subtitle":[],"editor":[{"given":"Daniel","family":"Bush","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,7,5]]},"references-count":44,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1012259","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pcbi.1012259","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,5]]}}}