1. Academic Validation
  2. Neuroinflammation induces anxiety- and depressive-like behavior by modulating neuronal plasticity in the basolateral amygdala

Neuroinflammation induces anxiety- and depressive-like behavior by modulating neuronal plasticity in the basolateral amygdala

  • Brain Behav Immun. 2021 Jan;91:505-518. doi: 10.1016/j.bbi.2020.11.007.
Zhi-Heng Zheng 1 Jiang-Long Tu 2 Xiao-Han Li 3 Qing Hua 3 Wei-Zhu Liu 1 Yu Liu 4 Bing-Xing Pan 1 Ping Hu 5 Wen-Hua Zhang 6
Affiliations

Affiliations

  • 1 Laboratory of Fear and Anxiety Disorders, Institutes of Life Science, Nanchang University, Nanchang 330031, PR China.
  • 2 Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, PR China.
  • 3 Department of Clinic Medicine, School of Queen Mary, Nanchang University, Nanchang, PR China.
  • 4 Rehabilitation Department, Second Affiliated Hospital of Nanchang University, PR China.
  • 5 Institute of Translational Medicine, Nanchang University, Nanchang 330001, PR China.
  • 6 Laboratory of Fear and Anxiety Disorders, Institutes of Life Science, Nanchang University, Nanchang 330031, PR China. Electronic address: whzhang@ncu.edu.cn.
Abstract

Increasing evidence indicates that excessive inflammatory responses play a crucial role in the pathophysiology of psychiatric diseases, including depression and anxiety disorders. The dysfunctional neural plasticity in amygdala has long been proposed as the vital cause for the progression of psychiatric disorders. However, the effect of neuroinflammation on the functional changes of the amygdala remains largely unknown. Here, by using a mouse model of inflammation induced by lipopolysaccharide (LPS) injection, we investigated the effect of LPS-induced neuroinflammation on the synaptic and non-synaptic plasticity in basolateral amygdala (BLA) projection neurons (PNs) and their contribution to the LPS-induced anxiety- and depressive-like behavior. The results showed that LPS treatment led to the activation of microglia and production of proinflammatory cytokines in the BLA. Furthermore, LPS treatment increased excitatory but not inhibitory synaptic transmission due to the enhanced presynaptic glutamate release, thus leading to the shift of excitatory/inhibitory balance towards excitatory. In addition, the intrinsic neuronal excitability of BLA PNs was also increased by LPS treatment through the loss of expression and function of small-conductance, calcium-activated Potassium Channel. Chronic fluoxetine pretreatment significantly prevented these neurophysiological changes induced by LPS, and alleviated anxiety and depressive-like behavior, indicating that LPS-induced neuronal dysregulation of BLA PNs may contribute to the development of psychiatry disorders. Collectively, these findings provide evidence that dysregulation of synaptic and non-synaptic transmission in the BLA PNs may account for neuroinflammation-induced anxiety- and depressive-like behavior.

Keywords

Amygdala; Anxiety; Depression; Neural plasticity; Neuroinflammation.

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