Neuronal Oscillation Dynamics Fmr1 KO2 mice
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Description: In vitro and ex vivo studies have shown consistent indications of hyperexcitability in the Fmr1 KO mouse model of autism spectrum disorder. We recently introduced a method to quantify network-level functional E/I ratio (fEI) from the neuronal oscillations. Here, we used this measure to study whether the implicated synaptic E/I disturbances translate to disturbances in network physiology in the Fmr1 KO model. We performed wireless skull-EEG recordings in wildtype (WT) and knockout (KO) male mice of the Fmr1 KO2 line in two separate experiments as an internal replication. Vigilance-state scoring was used to extract segments of inactive wakefulness as an equivalent behavioural condition to the human resting-state and, subsequently, we performed high-frequency resolution analysis of the fE/I biomarker, long-range temporal correlations (LRTC), and spectral power. We corroborated earlier studies showing increased high-frequency power in Fmr1 KO mice. LRTCs were higher in the gamma frequency ranges. Contrary to expectations, fEI was lower in the KO mice in high frequency ranges, suggesting more inhibition-dominated networks. Exposure to the GABA-agonist clonazepam decreased the fEI in both genotypes, confirming that increasing inhibitory tone results in a reduction of fEI. In addition, clonazepam decreased EEG power and increased LRTCs. These findings show applicability of these new resting-state EEG biomarkers to animal models for translational studies. They allow investigation of the effects of lower-level disturbances in E/I balance in relation to the organization of mass brain activity and how these may result in counterintuitive dynamics.