Modeling the impact of neuromorphological alterations in Down syndrome on fast neural oscillations

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• dc.contributor.author Clusella, Pau
• dc.contributor.author Manubens-Gil, Linus, 1989-
• dc.contributor.author García Ojalvo, Jordi
• dc.contributor.author Dierssen, Mara
• dc.date.accessioned 2024-09-18T06:26:08Z
• dc.date.available 2024-09-18T06:26:08Z
• dc.date.issued 2024
• dc.description.abstract 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 (∼40 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.
• dc.description.sponsorship PC and JGO have received funding from the Future and Emerging Technologies Programme (FET) of the European Union’s Horizon 2020 research and innovation programme (project NEUROTWIN, grant agreement No 101017716). JGO was also financially supported by the Spanish Ministry of Science and Innovation (project reference PID2021-127311NB-I00), the FEDER funds of the Spanish State Research Agency (project reference MICIN/AEI/10.13039/501100011033/FEDER), the Maria de Maeztu Programme for Units of Excellence in R\&D of the Spanish State Research Agency (project reference CEX2018-000792-M), and by the ICREA Academia program. LMG was supported by the National Natural Science Foundation of China (RFIS-I grant, reference 32350410413). MD acknowledges financial support from the Spanish Ministry of Science and Innovation (projects CPP2022-009659 and RTC2019-007329-1), the Spanish State Research Agency (project INTO-DS, reference PID2022-141900OB-I00), the Marato-TV3 Foundation (202212-30-31-32), and the European Comission Horizon 2020 programme (projects H2020-899986 and GO-DS21-848077). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• dc.format.mimetype application/pdf
• dc.identifier.citation Clusella P, Manubens-Gil L, Garcia-Ojalvo J, Dierssen M. Modeling the impact of neuromorphological alterations in Down syndrome on fast neural oscillations. PLoS Comput Biol. 2024 Jul 5;20(7):e1012259. DOI: 10.1371/journal.pcbi.1012259
• dc.identifier.doi http://dx.doi.org/10.1371/journal.pcbi.1012259
• dc.identifier.issn 1553-734X
• dc.identifier.uri http://hdl.handle.net/10230/61135
• dc.language.iso eng
• dc.publisher Public Library of Science (PLoS)
• dc.relation.ispartof PLoS Comput Biol. 2024 Jul 5;20(7):e1012259
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/101017716
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-127311NB-I00
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/CPP2022-009659
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTC2019-007329-1
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2022-141900OB-I00
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/899986
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/848077
• dc.rights © 2024 Clusella et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Neurons
• dc.subject.keyword Neuronal dendrites
• dc.subject.keyword Neural networks
• dc.subject.keyword Interneurons
• dc.subject.keyword Mouse models
• dc.subject.keyword Single neuron function
• dc.subject.keyword Animal models
• dc.subject.keyword Axons
• dc.title Modeling the impact of neuromorphological alterations in Down syndrome on fast neural oscillations
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion