Role of the habenulo-interpeduncular system in the neurodevelopmental basis of susceptibility and resilience to stress-induced anxiety

Experiencing stress during sensitive periods of brain development has a major impact on how individuals cope with later stress. Although many become more prone to develop anxiety or depression, some appear resilient. The mechanisms underlying these differences are unknown. Key answers may lie in how genetic and environmental stressors interact to shape the circuits controlling emotions. Here we studied the role of the habenulo-interpeducuncular system (HIPS), a critical node of reward circuits, in early stress-induced anxiety. We found that a subcircuit of this system, characterized by Otx2 expression, is particularly responsive to chronic stress during puberty, which induces HIPS hypersensitivity to later stress and susceptibility to develop anxiety. We further show that Otx2 deletion restricted to the HIPS counteracts these effects of stress. Together, these results demonstrate that Otx2 and stress interact, around puberty, to shape the HIPS stress-response, revealed here as a key modulator of susceptibility/resilience to develop anxiety.

Inference for cumulative risk model under step-stress experiments and its application in nanocrystalline data

With the popularity of step-stress accelerated life testing, researchers are exploring more possibilities for models that relate the life distributions under different stress levels. Cumulative risk model assumes that the effects of stress changes have a lag period before they are fully observed, which guarantees the continuity of the hazard rate function. This paper studies the cumulative risk model for Lomax distribution with step-stress experiments. For maximum likelihood estimation, Newton-Rapson method is adopted to get point estimates. Meanwhile, the asymptotic normality of the maximum likelihood estimator is used to obtain asymptotic confidence intervals. For Bayesian estimation, point estimates and highest posterior density credible intervals under squared error loss function with informative prior and non-informative prior are derived using Metropolis-Hastings method and Metropolis-Hastings within Gibbs algorithm. To evaluate the effects of stress change time and the length of lag period, as well as the performance of different methods, numerical simulations are conducted. Then a real nanocrystalline data set is analyzed.

Role of the habenulo-interpeduncular system in the neurodevelopmental basis of susceptibility and resilience to stressinduced anxiety

Experiencing stress during sensitive periods of brain development has a major impact on how individuals cope with later stress. Although many become more prone to develop anxiety or depression, some appear resilient. The mechanisms underlying these differences are unknown. Key answers may lie in how genetic and environmental stressors interact to shape the circuits controlling emotions. Here we studied the role of the habenulo-interpeducuncular system (HIPS), a critical node of reward circuits, in early stress-induced anxiety. We found that a subcircuit of this system, characterized by Otx2 expression, is particularly responsive to chronic stress during puberty, which induces HIPS hypersensitivity to later stress and susceptibility to develop anxiety. We further show that Otx2 deletion restricted to the HIPS counteracts these effects of stress. Together, these results demonstrate that Otx2 and stress interact, around puberty, to shape the HIPS stress-response, revealed here as a key modulator of susceptibility/resilience to develop anxiety.