Effects of different patterns of electric stimulation of the ventromedial prefrontal cortex on hippocampal-prefrontal coherence in a rat model of depression

Deep brain stimulation (DBS) is currently being studied as a promising treatment for treatment-refractory depression. However, the optimal pattern of stimulation and the underlying mechanism remain unknown. Neuronal communication between the hippocampus and ventral medial prefrontal cortex (vmPFC) may play an important role in emotional processes relevant to depression. Here, we investigated the effect of two commonly used patterns of vmPFC stimulation: high-frequency stimulation with low intensity (HFS, 130 Hz, 100 mu A) and low-frequency stimulation with high intensity (LFS, 20 Hz, 400 mu A), on oscillatory network dynamics in these two depression-related brain areas, in freely-moving rats after chronic unpredictable stress (CUS). We found that one hour of either LFS or HFS of the vmPFC induced a clear antidepressant-like effect in CUS rats. Analysis of local field potential (LFP) oscillation results showed that baseline power values were lower in CUS rats than normal controls, in the beta and gamma frequency range. Both HFS and LFS produced a widespread increase in spontaneous LFP oscillations, especially beta and gamma oscillations, in vmPFC and hippocampus of control and CUS rats. Furthermore, both HFS and LFS increased coordinated activity in beta and gamma bands between these two regions in freely-moving rats. In addition, there was no difference between LFS and HFS in the antidepressant-like response and LFP oscillations. These results suggest that HFS and LFS may share a common antidepressant mechanism, in which the augmentation of beta and gamma synchrony in vmPFC and hippocampus may contribute to the improvement of depressive-like behaviors.