TY - JOUR T1 - Increased excitation-inhibition ratio stabilizes synapse and circuit excitability in four autism mouse models JF - bioRxiv DO - 10.1101/317693 SP - 317693 AU - Michelle W. Antoine AU - Philipp Schnepel AU - Tomer Langberg AU - Daniel E. Feldman Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/05/09/317693.abstract N2 - Distinct genetic forms of autism are hypothesized to share a common increase in excitation-inhibition (E-I) ratio in cerebral cortex, causing hyperexcitability and excess spiking. We provide the first systematic test of this hypothesis across 4 mouse models (Fmr1−/y, Cntnap2−/-, 16p11.2del/+, Tsc2+/-), focusing on somatosensory cortex. All autism mutants showed reduced feedforward inhibition in layer 2/3 coupled with more modest, variable reductions in feedforward excitation, driving a common increase in E-I conductance ratio. Despite this, feedforward spiking, synaptic depolarization and spontaneous spiking were essentially normal. Modeling revealed that E and I conductance changes in each mutant were quantitatively matched to yield stable, not increased, synaptic depolarization for cells near spike threshold. Correspondingly, whisker-evoked spiking was not increased in vivo, despite detectably reduced inhibition. Thus, elevated E-I ratio is a common circuit phenotype, but appears to reflect homeostatic stabilization of synaptic drive, rather than driving network hyperexcitability in autism. ER -