RT Journal Article
SR Electronic
T1 Multidimensional imbalances in cortical circuit activity in Fragile-X Syndrome mice
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/2017/03/27/086363.abstract
AB A leading theory for multiple neurodevelopmental brain disorders holds that they arise from imbalances in excitatory and inhibitory (E/I) brain circuitry. However this theory has rarely been quantitatively tested. Here we combined computational modeling and analysis of in vivo 2-photon Ca2+ imaging data from cortex of wild-type and Fmr1 knock-out (KO) mice 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) greatly varying effects of synaptic and cellular properties on network activity; 3) 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, but an opposite increase in adult Fmr1 KO mice. These findings suggest qualitatively new strategies for understanding circuit alterations in Fragile-X Syndrome and related disorders.