Central role of regular firing neurons of centrolateral amygdala in affective behaviors

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-05-13 DOI:10.1016/j.isci.2025.112649

Alvaro García , M. Isabel Aller , Ana V. Paternain , Juan Lerma

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Abstract

Anxiety and depression are highly prevalent psychiatric disorders with poorly understood neural mechanisms. The amygdala, particularly its hyperactivity, is strongly implicated in anxiety. Mice overexpressing the Grik4 gene display anxiety, depression, social deficits, and disrupted amygdala excitability, inducing output circuit imbalance. To dissect the role of specific amygdala neuron populations, we created mice with extra copies of Grik4 and floxed native alleles. We normalized Grik4 dosage selectively in the basolateral amygdala (BLA) pyramidal cells via stereotaxic injection of AAV-CRE-GFP, using AAV-GFP as a control. Electrophysiological recordings from centrolateral amygdala (CeL) revealed that the normalization of Grik4 restored synaptic strength in regular but not late firing neurons. Behaviorally, this intervention reversed anxiety, depression, and social deficits, but not object recognition memory impairments. These results highlight the critical role of regular firing CeL neurons in affective disorders and suggest that targeting their activity may offer new strategies for treating anxiety and depression.

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杏仁核中央外侧正常放电神经元在情感行为中的核心作用

焦虑和抑郁是非常普遍的精神疾病，人们对其神经机制知之甚少。杏仁核，尤其是它的过度活跃，与焦虑密切相关。过度表达Grik4基因的小鼠表现出焦虑、抑郁、社交缺陷和杏仁核兴奋性紊乱，导致输出电路失衡。为了剖析特定杏仁核神经元群体的作用，我们制造了带有额外的Grik4拷贝和固定的天然等位基因的小鼠。以AAV-GFP为对照，通过立体定向注射，选择性地标准化了基底外侧杏仁核（BLA）锥体细胞中Grik4的剂量。来自中央外侧杏仁核（CeL）的电生理记录显示，Grik4的正常化恢复了正常而非晚发神经元的突触强度。在行为上，这种干预逆转了焦虑、抑郁和社交缺陷，但对物体识别记忆障碍没有作用。这些结果强调了正常放电的细胞神经元在情感障碍中的关键作用，并表明靶向它们的活动可能为治疗焦虑和抑郁提供新的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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