Early Life Stress Induces Different Behaviors in Adolescence and Adulthood May Related With Abnormal Medial Prefrontal Cortex Excitation/Inhibition Balance.

Yiwen Chen,Wei-Wei Su,Xuan Zeng,Wenwen Li,Lin Yao,Shaoyi Zheng,Chuanan Zhu,Yongjun Chen,Jinglan Yan,Yucen Xia,Yuanjia Zheng

doi:10.3389/fnins.2021.720286

Abstract

Early life stress is thought to be a risk factor for emotional disorders, particularly depression and anxiety. Although the excitation/inhibition (E/I) imbalance has been implicated in neuropsychiatric disorders, whether early life stress affects the E/I balance in the medial prefrontal cortex at various developmental stages is unclear. In this study, rats exposed to maternal separation (MS) that exhibited a well-established early life stress paradigm were used to evaluate the E/I balance in adolescence (postnatal day P43–60) and adulthood (P82–100) by behavior tests, whole-cell recordings, and microdialysis coupled with high performance liquid chromatography-mass spectrometry (HPLC-MS) analysis. First, the behavioral tests revealed that MS induced both anxiety- and depressive-like behaviors in adolescent rats but only depressive-like behavior in adult rats. Second, MS increased the action potential frequency and E/I balance of synaptic transmission onto L5 pyramidal neurons in the prelimbic (PrL) brain region of adolescent rats while decreasing the action potential frequency and E/I balance in adult rats. Finally, MS increases extracellular glutamate levels and decreased the paired-pulse ratio of evoked excitatory postsynaptic currents (EPSCs) of pyramidal neurons in the PrL of adolescent rats. In contrast, MS decreased extracellular glutamate levels and increased the paired-pulse ratio of evoked EPSCs of pyramidal neurons in the PrL of adult rats. The present results reveal a key role of E/I balance in different MS-induced disorders may related to the altered probability of presynaptic glutamate release at different developmental stages.

Highlights

Life is a critical period for brain development, both in humans and rodents, during which neuronal plasticity, synaptic organization, and remodeling activities rapidly develop (Di Segni et al, 2018)
In our maternal separation (MS) model, rats exhibited anxiety-like behaviors in adolescence (Figures 1B–E), which is consistent with other studies that used the same animal model (Banqueri et al, 2017; Auth et al, 2018)
Studies have shown that MS results in an elevated stress response and depressive-like behavior in adolescent rats, which is consistent with our study

Summary

Introduction

Life is a critical period for brain development, both in humans and rodents, during which neuronal plasticity, synaptic organization, and remodeling activities rapidly develop (Di Segni et al, 2018). The balance between excitatory and inhibitory synaptic transmission (E/I) is essential to ensure proper information processing and maintain a finely tuned balance in neural activity, which is vital for central physiological functions (Barden, 2004; Luscher et al, 2011). E/I imbalance contributes to numerous neuropsychiatric phenotypes, including anxiety, depression, and epilepsy (Yuen et al, 2012; Li et al, 2017; Czeh et al, 2018; Ghosal et al, 2020; Kim Y. et al, 2020); the effects of early stress on E/I balance at different developmental stages are still unclear

Methods

Results

Conclusion