Dataset Information

EphB2 in the Medial Prefrontal Cortex Regulates Vulnerability to Stress.

ABSTRACT: The ephrin B2 (EphB2) receptor is a tyrosine kinase receptor that is associated with synaptic development and maturation. It has recently been implicated in cognitive deficits and anxiety. However, still unknown is the involvement of EphB2 in the vulnerability to stress. In the present study, we observed decreases in EphB2 levels and their downstream molecules in the medial prefrontal cortex (mPFC) but not in the orbitofrontal cortex (OFC) in mice that were susceptible to chronic social defeat stress. The activation of EphB2 receptors with EphrinB1-Fc in the mPFC produced stress-resistant and antidepressant-like behavioral effects in susceptible mice that lasted for at least 10 days. EphB2 receptor knockdown by short-hairpin RNA in the mPFC increased the susceptibility to stress and induced depressive-like behaviors in a subthreshold chronic social defeat stress paradigm. These behavioral effects were associated with changes in the phosphorylation of cofilin and membrane ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking and the expression of some synaptic proteins in the mPFC. We also found that EphB2 regulated stress-induced spine remodeling in the mPFC. Altogether, these results indicate that EphB2 is a critical regulator of stress vulnerability and might be a potential target for the treatment of depression.

SUBMITTER: Zhang RX

PROVIDER: S-EPMC4987853 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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EphB2 in the Medial Prefrontal Cortex Regulates Vulnerability to Stress.

Zhang Ruo-Xi RX Han Ying Y Chen Chen C Xu Ling-Zhi LZ Li Jia-Li JL Chen Na N Sun Cheng-Yu CY Chen Wen-Hao WH Zhu Wei-Li WL Shi Jie J Lu Lin L

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20160422 10

The ephrin B2 (EphB2) receptor is a tyrosine kinase receptor that is associated with synaptic development and maturation. It has recently been implicated in cognitive deficits and anxiety. However, still unknown is the involvement of EphB2 in the vulnerability to stress. In the present study, we observed decreases in EphB2 levels and their downstream molecules in the medial prefrontal cortex (mPFC) but not in the orbitofrontal cortex (OFC) in mice that were susceptible to chronic social defeat s ...[more]

PMID: 27103064

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Project description:Previous neuroimaging studies have suggested that the experience of flow aligns with a relative increase in activation of the dorsal raphe nucleus (DRN), and relative activation decreases of the medial prefrontal cortex (MPFC) and of the amygdala (AMY). In the present study, Dynamic Causal Modeling (DCM) was used to explore effective connectivity between those brain regions. To test our hypothesis that the DRN causally down-regulates activity of the MPFC and/or of the AMY, 23 healthy male students solved mental arithmetic tasks of varying difficulty during functional magnetic resonance imaging. A "flow" condition, with task demands automatically balanced with participants' skill level, was compared with conditions of "boredom" and "overload". DCM models were constructed modeling full reciprocal endogenous connections between the DRN, the MPFC, the AMY, and the calcarine. The calcarine was included to allow sensory input to enter the system. Experimental conditions were modeled as exerting modulatory effects on various possible connections between the DRN, the MPFC, and the AMY, but not on self-inhibitory connections, yielding a total of 64 alternative DCM models. Model space was partitioned into eight families based on commonalities in the arrangement of the modulatory effects. Random effects Bayesian Model Selection (BMS) was applied to identify a possible winning family (and model). Although BMS revealed a clear winning family, an outstanding winning model could not be identified. Therefore, Bayesian Model Averaging was performed over models within the winning family to obtain representative DCM parameters for subsequent analyses to test our hypothesis. In line with our expectations, Bayesian averaged parameters revealed stronger down-regulatory influence of the DRN on the MPFC when participants experienced flow relative to control conditions. In addition, these condition-dependent modulatory effects significantly predicted participants' experienced degree of flow. The AMY was down-regulated irrespective of condition. The present results suggest a causal role for the DRN in modulating the MPFC, contributing to the experience of flow.

Dataset Information

EphB2 in the Medial Prefrontal Cortex Regulates Vulnerability to Stress.

Publications

EphB2 in the Medial Prefrontal Cortex Regulates Vulnerability to Stress.

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