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.

中文翻译：

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神经炎症通过调节基底外侧杏仁核的神经元可塑性诱导焦虑和抑郁样行为

越来越多的证据表明，过度的炎症反应在精神疾病（包括抑郁症和焦虑症）的病理生理学中起着至关重要的作用。长期以来，杏仁核中功能失调的神经可塑性一直被认为是精神疾病进展的重要原因。然而，神经炎症对杏仁核功能变化的影响在很大程度上仍然未知。在这里，通过使用脂多糖 (LPS) 注射诱导的炎症小鼠模型，我们研究了 LPS 诱导的神经炎症对基底外侧杏仁核 (BLA) 投射神经元 (PNs) 突触和非突触可塑性的影响及其对LPS 引起的焦虑和抑郁样行为。结果表明，LPS 治疗导致 BLA 中小胶质细胞的激活和促炎细胞因子的产生。此外，由于突触前谷氨酸释放增加，LPS 治疗增加了兴奋性而非抑制性突触传递，从而导致兴奋性/抑制性平衡向兴奋性转变。此外，LPS 治疗还通过小电导钙激活钾通道的表达和功能丧失来增加 BLA PNs 的内在神经元兴奋性。慢性氟西汀预处理显着阻止了 LPS 诱导的这些神经生理学变化，并减轻了焦虑和抑郁样行为，表明 LPS 诱导的 BLA PN 神经元失调可能有助于精神疾病的发展。总的来说，