Relationship Between Dentate Gyrus Oscillation In Hippocampus And Depression-like Behavior

Depressive disorder is a prevalent mental disorder,and its high rates of disability and suicide impose a significant burden on society and families.However,the pathogenesis of depressive disorder is largely unknown yet,and there are no specific clinical indicators.As one of the brain regions that are greatly affected in the pathogenesis of depressive disorder,hippocampus is inseparable from the emotional changes in the onset of depressive disorder,but it is still unclear which changes in neural activity in the hippocampus are directly related to the state of depression.Our research focuses on the changes of hippocampal oscillation activities in the development of depressive disorder and after anti-depressive treatment.Since stress is one of the key factors leading to depressive disorder,we used a chronic unpredictable mild stress mouse model and a deep brain stimulation treatment model of nucleus accumbens,and used behavioral measures to detect the degree of depression in mice and the degree of recovery after treatment.The multi-channel electrophysiological technique was used to record the local field potential changes in the dorsal hippocampal dentate gyrus during the process of depression and recovery in mice,and the different frequency bands of hippocampal oscillation were subdivided for statistical analysis.Finally,immunohistochemical staining was used to determine whether the change of number of PV-positive interneurons in the dorsal hippocampal dentate gyrus of mice was involved in the intrinsic mechanism of neuronal oscillation.The results of our study found that: 1)14 days of chronic unpredictable mild stress will induce depression-like behavior in some mice,while 7 days of deep brain stimulation of nucleus accumbens will alleviate depression in mice;2)Acute stress will cause a decrease in the activity of the high gamma oscillation(50-100 Hz)in the dorsal hippocampal dentate gyrus,which will be recovered after the end of acute stress;3)The degree of depression caused by chronic stress increases,while the high gamma oscillation activity of the dorsal hippocampal dentate gyrus is weakened.And the high gamma oscillation activity increased after deep brain stimulation of nucleus accumbens anti-depressive treatment;4)The number of PV-positive interneurons in the dorsal hippocampal dentate gyrus decreased in depressed mice and recovered after deep brain stimulation of nucleus accumbens anti-depressive treatment.Conclusion: We have successfully established a chronic unpredictable mild stress and deep brain stimulation treatment mice model,which provides an animal model basis for future related research.It was found that high gamma oscillation activity is closely related to acute and chronic stress in mice and may be a potential biomarker of stress.In addition,we also found that changes in the degree of depression,high gamma oscillations,and the number of PV-positive interneurons in mice are interrelated,which provides a neuroelectrophysiological-related basis for the study of the pathogenesis of depression,as well as a potential biomarker for the diagnosis and treatment effect of depression.