| First Author | Antoine MW | Year | 2019 |
| Journal | Neuron | Volume | 101 |
| Issue | 4 | Pages | 648-661.e4 |
| PubMed ID | 30679017 | Mgi Jnum | J:271893 |
| Mgi Id | MGI:6282272 | Doi | 10.1016/j.neuron.2018.12.026 |
| Citation | Antoine MW, et al. (2019) Increased Excitation-Inhibition Ratio Stabilizes Synapse and Circuit Excitability in Four Autism Mouse Models. Neuron 101(4):648-661.e4 |
| abstractText | 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 a systematic test of this hypothesis across 4 mouse models (Fmr1(-/y), Cntnap2(-/-), 16p11.2(del/+), Tsc2(+/-)), focusing on somatosensory cortex. All autism mutants showed reduced feedforward inhibition in layer 2/3 coupled with more modest, variable reduction in feedforward excitation, driving a common increase in E-I conductance ratio. Despite this, feedforward spiking, synaptic depolarization, and spontaneous spiking were largely 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. |
