Abstract
Sleep disturbances affect up to 80% of children with autism spectrum disorder (ASD). While these deficits have been extensively documented, the underlying sleep neurophysiological changes remain largely unknown. Human investigations are limited to EEG recordings, but rodents provide a tractable mammalian model to probe cellular and network level neuronal activity, since key sleep rhythms, such as cortical slow oscillations (SO), thalamocortical spindles, and hippocampal sharp-wave ripples (SWRs), are conserved. Synchronization of these rhythms/oscillations during non-rapid eye movement (NREM) sleep supports memory consolidation, and the coordination within this network supports sleep stability and continuity. Thus, to test if sleep deficits in ASD are associated with dysfunctional circuit coordination, we conducted high-density electrophysiological recordings in the hippocampus and prefrontal cortex of wild-type (WT) and Fmr1 rats during sleep. Fmr1 rats, a model of Fragile X syndrome, displayed more fragmented NREM sleep and aberrant coupling between SOs, spindles, and SWRs compared to WT rats. Single neuron activity in Fmr1 rats in both regions showed a pronounced lack of SO-mediated firing rate modulation and SO entrainment. With the advent of therapeutic neuromodulation, these findings can elucidate mechanisms for disordered sleep in ASD and identify biomarkers to guide the development of effective interventions.