Low-intensity focused ultrasound ameliorates depression-like behaviors associated with improving the synaptic plasticity in the vCA1-mPFC pathway

It is of great social significance and clinical value to explore new effective treatments for depression. Low-intensity focused ultrasound stimulation (LIFUS) has been indicated to have notable neuroprotective effects on depression. However, little is known about how different strategies of LIFUS affect the therapeutic effect. Therefore, the purpose of this study is to investigate whether the effects of LIFUS on depression-like behaviors are associated with the intensity and the underlying mechanisms. We established the depression rats model using the chronic unpredictable stress (CUS) and applied the LIFUS with high/low intensity (Ispta = 500 and 230 mW/cm2, respectively) to the left medial prefrontal cortex (mPFC) after CUS. We found that two intensities of LIFUS both could significantly improve depression-like behaviors to a comparable degree. We further found that theta oscillation synchronization and synaptic functional plasticity in the hippocampal vCA1-mPFC pathway were significantly improved by chronic LIFUS which mainly due to the alternation of synaptic structural plasticity and the expression of post-synaptic proteins in the mPFC. These results suggest that LIFUS ameliorates the depression-like behaviors associated with improving the synaptic plasticity in the vCA1-mPFC pathway. Our study provides preclinical evidence and a theoretical basis for applying LIFUS for depression treatment.