Beyond excitation/inhibition imbalance in multidimensional models of neural circuit changes in brain disorders
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- Cian O'Donnell
- Department of Computer Science, University of Bristol, Bristol, United Kingdom
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- J Tiago Gonçalves
- Dominick Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, United States
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- Carlos Portera-Cailliau
- Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, United States
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- Terrence J Sejnowski
- Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States
説明
<jats:p>A leading theory holds that neurodevelopmental brain disorders arise from imbalances in excitatory and inhibitory (E/I) brain circuitry. However, it is unclear whether this one-dimensional model is rich enough to capture the multiple neural circuit alterations underlying brain disorders. Here, we combined computational simulations with analysis of in vivo two-photon Ca<jats:sup>2+</jats:sup> imaging data from somatosensory cortex of <jats:italic>Fmr1</jats:italic> knock-out (KO) mice, a model of Fragile-X Syndrome, to test the E/I imbalance theory. We found that: (1) The E/I imbalance model cannot account for joint alterations in the observed neural firing rates and correlations; (2) Neural circuit function is vastly more sensitive to changes in some cellular components over others; (3) The direction of circuit alterations in <jats:italic>Fmr1</jats:italic> KO mice changes across development. These findings suggest that the basic E/I imbalance model should be updated to higher dimensional models that can better capture the multidimensional computational functions of neural circuits.</jats:p>
収録刊行物
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- eLife
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eLife 6 e26724-, 2017-10-11
eLife Sciences Publications, Ltd
