Moderate maternal separation mitigates the altered synaptic transmission and neuronal activation in amygdala by chronic stress in adult mice

Xia Qin,Na Wang,Yong-Mei Zhang,Jia-Xin Zou,Jun-Li Cao,Ye He,Bing-Xing Pan,Wen-Hua Zhang

doi:10.1186/s13041-019-0534-4

Abstract

Exposure to moderate level of stress during the perinatal period helps the organisms to cope well with stressful events in their later life, an effect known as stress inoculation. Amygdala is one of the kernel brain regions mediating stress-coping in the brain. However, little is known about whether early life stress may affect amygdala to have its inoculative effect. Here, we observed that moderate maternal separation (MS) from postnatal day 3 to day 21 (D3–21, 1 h per day) significantly alleviated the increased anxiety-like behavior induced by chronic social defeat stress (CSDS) in adulthood, suggesting an obvious inoculative effect of moderate MS. Further studies revealed that MS prevented CSDS-evoked augmentation of glutamatergic transmission onto principal neurons (PNs) in the basolateral amygdala (BLA) by inhibiting presynaptic glutamate release. By contrast, it did not affect GABAergic transmission in BLA PNs, as indicated by unaltered frequency and amplitude of miniature inhibitory postsynaptic currents (mIPSCs). Moreover, the CSDS-induced increase of neuronal excitability was also mitigated by MS in BLA PNs. In conclusion, our results suggest that MS may have its inoculative effect through alleviating the influences of later life stress on the glutamatergic transmission and neuronal activity in amygdala neurons.

Highlights

The effects of stress on the brain and behavior often vary in a nonlinear manner, with the severity of stress roughly corresponding to an inverted U-shaped reaction norm
maternal separation (MS) ameliorates chronic social defeat stress (CSDS)-induced anxiety-like behavior in adult mice To assess whether early mild MS used in the present study had inoculative effect for the late-arriving stress in adult mice, we separated the mice into four groups (Fig. 1)
MS per se had little effect on the anxiety-like behavior of mice, as indicated by the unaltered behavioral parameters between the MS and control mice. It effectively mitigated the increased anxiety-like behavior induced by CSDS in adult mice (MS + CSDS vs. CSDS), as indicated by more open arm time (p = 0.0362, Fig. 2a, b) and more entries in Elevated plus maze (EPM) (p = 0.0271, Fig. 2a, c) and more time in the center square in Open field test (OFT) (p = 0.0147, Fig. 2d, e) in mice experiencing both MS and CSDS relative to those having CSDS only

Summary

Introduction

The effects of stress on the brain and behavior often vary in a nonlinear manner, with the severity of stress roughly corresponding to an inverted U-shaped reaction norm. Pre-weaning repeated, long-term maternal separation (i.e., 3–24 h, a severe stress) has been found to induce maladaptive behavioral changes such as anxiety [3], and deficits in associative learning. Research on the brain mechanisms of stress inoculation revealed that multiple brain regions including prefrontal cortex [13, 14], striatum [10] and hippocampus [15] are engaged in this process. In the anterior cingulate cortex (ACC), stress inoculation by intermittent

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