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bioRxiv · 10.1101/317693

Increased excitation-inhibition ratio stabilizes synapse and circuit excitability in four autism mouse models.

Antoine, M. W.·Schnepel, P.·Langberg, T.·Feldman, D. E.
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Abstract

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.

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Antoine, M. W., Schnepel, P., Langberg, T., Feldman, D. E.. 2018-05-09. Increased excitation-inhibition ratio stabilizes synapse and circuit excitability in four autism mouse models.. https://doi.org/10.1101/317693

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