Abnormal hippocampal theta and gamma hypersynchrony produces network and spike timing disturbances in the Fmr1-KO mouse model of Fragile X syndrome

Compared to wild type mice, Fmr1-KO mice displayed greater power of hippocampal theta oscillations, and higher coherence in the slow gamma band. Additionally, spike trains of Fmr1-KO interneurons show decreased spike-count correlations and they are hypersynchronized with theta and slow gamma oscillations. The hypersynchronization of Fmr1-KO oscillations and spike timing reflects functional deficits in local networks. This network hypersynchronization pathologically decreases the heterogeneity of spike-LFP phase coupling, compromising information processing within the hippocampal circuit. These findings may reflect a pathophysiological mechanism explaining cognitive impairments in FXS and autism, in which there is anomalous processing of social and environmental cues and associated deficits in memory and cognition.