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bioRxiv · 10.1101/086363

Multidimensional imbalances in cortical circuit activity in Fragile-X Syndrome mice

O'Donnell, C.·Goncalves, J. T.·Portera-Cailliau, C.·Sejnowski, T. J.
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Abstract

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.

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O'Donnell, C., Goncalves, J. T., Portera-Cailliau, C., Sejnowski, T. J.. 2016-11-07. Multidimensional imbalances in cortical circuit activity in Fragile-X Syndrome mice. https://doi.org/10.1101/086363

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