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Modeling the impact of neuromorphological alterations in Down syndrome on fast neural oscillations.
- Source :
-
PLoS computational biology [PLoS Comput Biol] 2024 Jul 05; Vol. 20 (7), pp. e1012259. Date of Electronic Publication: 2024 Jul 05 (Print Publication: 2024). - Publication Year :
- 2024
-
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.<br />Competing Interests: The authors have declared that no competing interests exist.<br /> (Copyright: © 2024 Clusella et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Subjects :
- Animals
Mice
Pyramidal Cells pathology
Pyramidal Cells physiology
Neurons physiology
Neurons pathology
Interneurons physiology
Interneurons pathology
Computer Simulation
Motor Cortex physiopathology
Motor Cortex pathology
Disease Models, Animal
Humans
Mice, Transgenic
Nerve Net physiopathology
Nerve Net pathology
Down Syndrome physiopathology
Down Syndrome pathology
Models, Neurological
Computational Biology
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7358
- Volume :
- 20
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- PLoS computational biology
- Publication Type :
- Academic Journal
- Accession number :
- 38968294
- Full Text :
- https://doi.org/10.1371/journal.pcbi.1012259