Disc1 gene down-regulation impaired synaptic plasticity and recognition memory via disrupting neural activity in mice

The gene of Disrupted-in-schizophrenia 1 (Disc1) is closely related to mental diseases with cognitive deficits, but there are few studies on the changes in neural oscillations and recognition memory. Neural oscillations plays a key role in the nervous system in a dynamic form, which is closely related to advanced cognitive activities such as information processing and memory consolidation. Hence, we aimed to investigate if Disc1 knockdown disrupted the normal pattern of neural activities in the mouse hippocampus network, and determined if quantitative neural oscillation approach could be a potential diagnostic tool for mental disorders. In the study, we reported that Disc1 gene, downregulated by short-hairpin RNA (shRNA), not only induced anxiety-like behavior and sociability impairment but also damaged both synaptic plasticity and recognition memory in mice. Moreover, Disc1 knockdown mice exhibited evidently abnormal power spectral distributions, reduced phase synchronizations, and decreased phase-amplitude coupling strength compared to that of normal animals. In addition, transcriptome analyses showed that there were clearly transcriptional changes in Disc1 knockdown mice. Altogether, our findings suggest that the abnormal pattern of neural activities in the hippocampus network disrupts information processing and finally leads to the impairments of synaptic plasticity and recognition in Disc1 knockdown mice, which are possibly associated with the obstruction of neurotransmitter transmission. Importantly, the data imply that the analysis of neural oscillation pattern provides a potential diagnosis approach for mental disorders.