Behavioral state-dependent oscillatory activity in prefrontal cortex induced by chronic social defeat stress.

Chronic stress contributes to the onset and exacerbation of major depressive disorder (MDD) through the oscillatory activity in the prefrontal cortex (PFC). However, the oscillations on which chronic social stress converges to yield the behavioral state of social avoidance are largely unknown. Here, we use a chronic social defeat stress model and in vivo electrophysiological recordings to uncover a novel neurophysiological measure that predicts the social behavioral state in stressed animals. First, in this study, we find that chronic social defeat stress model induces depression-like behaviors (anhedonia and social avoidance). Second, we find statistically significant differences in PFC oscillatory activity across different frequency ranges in social behavioral state, and the oscillatory activity correlates with stress-induced behavioral state. Finally, we show that the social behavioral states are accurately decoded from the oscillatory activity based on machine learning. Together, these results demonstrate that naturally occurring differences in PFC oscillation underlie the social behavioral state that accompanies the emergence of stress-induced behavioral dysfunction.

Information transmission in mPFC-BLA network during exploratory behavior in the open field.

Exploratory behavior plays a fundamental role in motivation, learning, and well-being of organisms. The open field test (OFT) is a classic method to investigate the exploratory behavior in rodents, also a widely adopted and pharmacologically validated procedure for evaluating anxiety and depression. Several lines of evidence have shown that medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) play crucial roles in anxiety-like or depression-like exploratory behavior. However, the dynamic characterization of the mPFC-BLA network in exploratory behavior is less well understood. Therefore, this study aimed to investigate the information transmission mechanism in the mPFC-BLA network during exploratory behavior. Local field potentials (LFPs) from mPFC and BLA were simultaneously recorded while the rats performed the OFT. Directed transfer function (DTF), which was derived from Granger causal connectivity analysis, was applied to measure the functional connectivity among LFPs. Information flow (IF) was calculated to explore the dynamics of information transmission in the mPFC-BLA network. Our results revealed that, for both mPFC and BLA, the theta-band functional connectivity in periphery was significantly higher than that in center of the open field. The IF from BLA to mPFC in the open field task was significantly higher than that from mPFC to BLA. These results suggest that the functional connectivity and IF in the mPFC-BLA network are related to the exploratory behavior, and information transmission from BLA to mPFC could be predominant for exploratory behavior.

Reduced Information Transmission of Medial Prefrontal Cortex to Basolateral Amygdala Inhibits Exploratory Behavior in Depressed Rats.

Depression is a mental and neurological disease that reduces the desire for exploration. Dysregulation of the information transmission between medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) is associated with depression. However, which direction of information transmission (mPFC-BLA or BLA-mPFC) related to the decline of exploratory interests in depression is unclear. Therefore, it is important to determine what specific changes occur in mPFC and BLA information transmission in depressed rats during exploratory behavior. In the present study, local field potentials (LFPs) were recorded via multi-electrodes implanted in the mPFC and BLA for the control and depression groups of rats when they were exploring in an open field. The theta band was determined to be the characteristic band of exploratory behavior. The direct transfer function (DTF) was used to calculate the mPFC and BLA bidirectional information flow (IF) to measure information transmission. Compared with the control group, the theta IF of mPFC-BLA in the depression group was significantly reduced, and there was no significant difference in theta IF of BLA-mPFC between the two groups. Our results indicated that the reduction of mPFC-BLA information transmission can inhibit the exploratory behavior of depressed rats.