Beyond excitation/inhibition imbalance in multidimensional models of neural circuit changes in brain disorders

Cian O’Donnell, J. Tiago Goncalves, Carlos Portera-Cailliau, Terrence J. Sejnowski

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 Ca2+ imaging data from somatosensory cortex of Fmr1 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 Fmr1 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.

Original languageEnglish (US)
Article numbere26724
JournaleLife
Volume6
DOIs
StatePublished - Oct 11 2017

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Brain Diseases
Knockout Mice
Brain
Fragile X Syndrome
Somatosensory Cortex
Networks (circuits)
Photons
Joints
Inhibition (Psychology)
Imaging techniques
Neurodevelopmental Disorders
Direction compound

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Beyond excitation/inhibition imbalance in multidimensional models of neural circuit changes in brain disorders. / O’Donnell, Cian; Goncalves, J. Tiago; Portera-Cailliau, Carlos; Sejnowski, Terrence J.

In: eLife, Vol. 6, e26724, 11.10.2017.

Research output: Contribution to journalArticle

O’Donnell, Cian ; Goncalves, J. Tiago ; Portera-Cailliau, Carlos ; Sejnowski, Terrence J. / Beyond excitation/inhibition imbalance in multidimensional models of neural circuit changes in brain disorders. In: eLife. 2017 ; Vol. 6.
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