Fear conditioning and extinction distinctively alter bidirectional synaptic plasticity within the amygdala of an animal model of post-traumatic stress disorder

IF 4.3 2区医学 Q1 NEUROSCIENCES

Neurobiology of Stress Pub Date : 2024-01-12 DOI:10.1016/j.ynstr.2024.100606

Kwanghoon Park, Hoyong Park, ChiHye Chung

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引用次数: 0

Abstract

Synaptic plasticity in the amygdala plays an essential role in the formation and inhibition of fear memory; however, this plasticity has mainly been studied in the lateral amygdala, making it largely uninvestigated in other subnuclei. Here, we investigated long-term potentiation (LTP) and long-term depression (LTD) in the basolateral amygdala (BLA) to the medial division of the central amygdala (CEm) synapses of juvenile C57BL/6N (B6) and 129S1/SvImJ (S1) mice. We found that in naïve B6 and S1 mice, LTP was not induced at the BLA to CEm synapses, whereas fear conditioning lowered the threshold for LTP induction in these synapses of both B6 and S1 mice. Interestingly, fear extinction disrupted the induction of LTP at the BLA to CEm synapses of B6 mice, whereas LTP was left intact in S1 mice. Both low-frequency stimulation (LFS) and modest LFS (mLFS) induced LTD in naïve B6 and S1 mice, suggesting that the BLA to CEm synapses express bidirectional plasticity. Fear conditioning disrupted both types of LTD induction selectively in S1 mice and LFS-LTD, presumably NMDAR-dependent LTD was partially recovered by fear extinction. However, mLFS-LTD which has been known to be endocannabinoid receptor 1 (CB1R)-dependent was not induced after fear extinction in both mouse strains. Our observations suggest that fear conditioning enhances LTP while fear extinction diminishes LTP at the BLA to the CEm synapses of B6 mice with successful extinction. Considering that S1 mice showed strong fear conditioning and impaired extinction, strong fear conditioning in the S1 strain may be related to disrupted LTD, and impaired extinction may be due to constant LTP and weak LFS-LTD at the BLA to CEm synapses. Our study contributes to the further understanding of the dynamics of synaptic potentiation and depression between the subnuclei of the amygdala in juvenile mice after fear conditioning and extinction.

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恐惧调节和消退会明显改变创伤后应激障碍幼年动物模型杏仁核内的双向突触可塑性

杏仁核中的突触可塑性在恐惧记忆的形成和抑制过程中起着至关重要的作用；然而，这种可塑性主要是在杏仁核外侧进行研究的，因此在其他亚核中基本上没有研究。在这里，我们研究了幼年 C57BL/6N (B6) 和 129S1/SvImJ (S1) 小鼠杏仁核基底外侧（BLA）到杏仁核中央内侧分部（CEm）突触的长期电位（LTP）和长期抑制（LTD）。我们发现，在天真的B6和S1小鼠中，BLA到CEm突触不会诱导LTP，而恐惧条件反射会降低B6和S1小鼠这些突触的LTP诱导阈值。有趣的是，恐惧消退会破坏B6小鼠BLA至CEm突触的LTP诱导，而S1小鼠的LTP则保持不变。低频刺激（LFS）和适度LFS（mLFS）都能在天真的B6和S1小鼠中诱导LTD，这表明BLA至CEm突触具有双向可塑性。在 S1 小鼠中，恐惧条件选择性地破坏了这两种类型的 LTD 诱导，而 LFS-LTD（推测为 NMDAR 依赖性 LTD）在恐惧消失后得到了部分恢复。然而，已知依赖于内源性大麻素受体 1（CB1R）的 mLFS-LTD 在两种小鼠品系的恐惧消退后都没有被诱导。我们的观察结果表明，恐惧条件反射会增强 LTP，而恐惧消退会降低成功消退的 B6 小鼠 BLA 至 CEm 突触的 LTP。考虑到S1小鼠表现出强烈的恐惧条件反射和消退障碍，S1品系的强烈恐惧条件反射可能与LTTP的破坏有关，而消退障碍可能是由于BLA到CEm突触的LTP不变和LFS-LTD减弱所致。我们的研究有助于进一步了解幼年小鼠在恐惧条件反射和消退后杏仁核亚核之间突触电位增强和抑制的动态变化。

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

Neurobiology of Stress Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

9.40

自引率

4.00%

发文量

审稿时长

48 days

期刊介绍： Neurobiology of Stress is a multidisciplinary journal for the publication of original research and review articles on basic, translational and clinical research into stress and related disorders. It will focus on the impact of stress on the brain from cellular to behavioral functions and stress-related neuropsychiatric disorders (such as depression, trauma and anxiety). The translation of basic research findings into real-world applications will be a key aim of the journal. Basic, translational and clinical research on the following topics as they relate to stress will be covered: Molecular substrates and cell signaling, Genetics and epigenetics, Stress circuitry, Structural and physiological plasticity, Developmental Aspects, Laboratory models of stress, Neuroinflammation and pathology, Memory and Cognition, Motivational Processes, Fear and Anxiety, Stress-related neuropsychiatric disorders (including depression, PTSD, substance abuse), Neuropsychopharmacology.