RT Journal Article
SR Electronic
T1 Beyond excitation/inhibition imbalance in multidimensional models of neural circuit changes in brain disorders
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 086363
DO 10.1101/086363
A1 Cian O’Donnell
A1 J. Tiago Gonçalves
A1 Carlos Portera-Cailliau
A1 Terrence J. Sejnowski
YR 2017
UL http://biorxiv.org/content/early/2017/09/08/086363.abstract
AB 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 onedimensional model is rich enough to capture the multiple neural circuit alterations underlying brain disorders. Here we combined computational simulations with analysis of in vivo 2-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.