The current results demonstrated that DA D2 receptors in the ACC are required for observational fear learning, whereas increased 5-HT levels disrupt observational fear and alter the regularity of ACC neural oscillations.

The establishment and maintenance of social dominance are critical for social stability and the survival and health of individual animals. Stress lead to depression and a decrease in the social status of depressed persons is a risk factor for suicide. Therefore, we explored the mechanistic and behavioral links among stress, depression, and social dominance and found that mice subjected to chronic restraint stress (CRS), an animal model of stress-induced depression, showed decreased social dominance as measured by a dominance tube test. Importantly, this submissive behavior was occluded by the antidepressant, fluoxetine, a selective serotonin reuptake inhibitor. It is known that social dominance is controlled by synaptic efficacy in the medial prefrontal cortex (mPFC) and that AMPA-type glutamate receptor (AMPA-R) is a key molecule for synaptic efficacy. We found that the phosphorylation on AMPA-R was bidirectionally changed by CRS and fluoxetine in the mPFC of mice with CRS. Moreover, we found a strong correlation between social dominance and AMPA-R phosphorylation that regulates synaptic efficacy by modulating the synaptic targeting of AMPA-R. Our correlational analysis of the behavior and biochemistry of the CRS model suggests that AMPA-R phosphorylation in the mPFC may serve as a biomarker of social dominance related to stress.

Emerging evidence indicates that cellular senescence could be a critical inducing factor for aging-associated neurodegenerative disorders. However, the involvement of cellular senescence remains unclear in Parkinson’s disease (PD). To determine this, we assessed the effects of α-synuclein preformed fibrils (α-syn PFF) or 1-methyl-4-phenylpyridinium (MPP+) on changes in cellular senescence markers, employing α-syn PFF treated-dopaminergic N27 cells, primary cortical neurons, astrocytes and microglia and α-syn PFF-injected mouse brain tissues, as well as human PD patient brains. Our results demonstrate that α-syn PFF-induced toxicity reduces the levels of Lamin B1 and HMGB1, both established markers of cellular senescence, in correlation with an increase in the levels of p21, a cell cycle-arrester and senescence marker, in both reactive astrocytes and microglia in mouse brains. Using Western blot and immunohistochemistry, we found these cellular senescence markers in reactive astrocytes as indicated by enlarged cell bodies within GFAP-positive cells and Iba1-positive activated microglia in α-syn PFF injected mouse brains. These results indicate that PFF-induced pathology could lead to astrocyte and/or microglia senescence in PD brains, which may contribute to neuropathology in this model. Targeting senescent cells using senolytics could therefore constitute a viable therapeutic option for the treatment of PD.

BackgroundDepression is one of the most prevalent mood disorders, and is known to be associated with abnormal functional connectivity in neural networks of the brain. Interestingly, a significant proportion of patients with depression experience spontaneous remission without any treatment. However, the relationship between electroencephalographic (EEG) functional connectivity and the spontaneous remission in depression remains poorly understood. Here, we investigated regional and network brain activity using EEG signals from a chronic restraint stress (CRS)-induced mouse model of depression. After 1 (CRS1W) or 3 weeks (CRS3W) following the cessation of a 4-week-long CRS, mice were subjected to depression-associated behavioral tasks. EEG signals were obtained from eight cortical regions (frontal, somatosensory, parietal, and visual cortices in each hemisphere).ResultsThe CRS1W group exhibited behavioral dysfunctions in the open field and forced swim tasks, whereas the CRS3W group displayed normal levels of behaviors in those tasks. In a linear correlation analysis, the CRS1W group exhibited increased correlation coefficient values at all frequency bands (delta, 1.5–4; theta, 4–8; alpha, 8–12; beta, 12–30; gamma, 30–80 Hz) compared with the control group. However, the differences in delta- and gamma-frequency bands between the control and CRS1W groups were no longer observed in the CRS3W group. Persistent brain network homology revealed significantly different functional connectivity between the control and CRS1W groups, and it demonstrated a huge restoration of the decreased distances in the gamma-frequency band for the CRS3W group. Moreover, the CRS3W group displayed a similar strength of connectivity among somatosensory and frontal cortices as the control group.ConclusionA mouse model of CRS-induced depression showed spontaneous behavioral remission of depressive behavior. Using persistent brain network homology analysis of EEG signals from eight cortical regions, we found that restoration of gamma activity at the network level is associated with behavioral remission.Electronic supplementary materialThe online version of this article (doi:10.1186/s12868-016-0239-x) contains supplementary material, which is available to authorized users.