%0 Journal Article %A Cian O’Donnell %A J. Tiago Gonçalves %A Carlos Portera-Cailliau %A Terrence J. Sejnowski %T Multidimensional imbalances in cortical circuit activity in Fragile-X Syndrome mice %D 2016 %R 10.1101/086363 %J bioRxiv %P 086363 %X A leading theory for multiple brain disorders, such as schizophrenia and autism, is that they arise from developmental imbalances in excitatory and inhibitory (E/I) brain circuitry. However, it is unclear whether this simple 1-dimensional model is sufficiently rich to capture the set of key alterations of neural circuit processing in brain disorders. Here we used a combination of computational modeling and large-scale analysis of in vivo 2-photon Ca2+ imaging data from somatosensory cortex of wild-type and Fmr1 knock-out (KO) mice, a model of Fragile X syndrome, to test the E/I imbalance model. Our main findings were: 1) the E/I imbalance model was not rich enough to capture the alterations in neural activity statistics in Fmr1 KO mice; 2) in a computational model we found greatly varying magnitudes and directions of effects of synaptic and cellular properties on network activity; 3) evidence for opposite changes in circuit properties of Fmr1 KO mice at different stages of development; 4) a reduction in the entropy of circuit activity in young Fmr1 KO mice compared to wild-type, but an opposite increase in adult Fmr1 KO mice. These findings suggest qualitatively new strategies for developing treatments for Fragile-X Syndrome and related disorders. %U https://www.biorxiv.org/content/biorxiv/early/2016/11/07/086363.full.pdf