杏仁核基底外侧回路的破坏支持抑郁状态下的负价值偏向。

IF 5.8 1区 医学 Q1 PSYCHIATRY
Mathilde Bigot, Claire-Hélène De Badts, Axel Benchetrit, Éléonore Vicq, Carine Moigneu, Manon Meyrel, Sébastien Wagner, Alexandru Adrian Hennrich, Josselin Houenou, Pierre-Marie Lledo, Chantal Henry, Mariana Alonso
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引用次数: 0

摘要

消极偏差是抑郁发作的一个基本特征,它导致患者对环境线索赋予更多的消极价值。这种负面偏差会影响包括情绪反应、注意力和记忆力在内的所有信息处理水平,从而导致抑郁症状的发展和维持。在这种情况下,令人愉快的刺激变得不那么有吸引力,而令人不愉快的刺激则更具厌恶性,但这种偏差背后的相关神经回路在很大程度上仍不为人所知。通过研究长期服用皮质酮(CORT)的抑郁症小鼠模型,我们发现嗅觉刺激的价值归因出现了负面偏差,而这种偏差会对抗抑郁药物产生反应。这一结果与我们在双相抑郁症患者身上观察到的气味价值分配的改变相一致。鉴于杏仁核在价值编码中的关键作用及其与抑郁症的密切联系,我们假设基底外侧杏仁核(BLA)回路的改变可能会支持与抑郁状态相关的负性转变。与人类不同的是,人类的成像工具空间分辨率有限,难以对杏仁核进行简单的分割,而最近揭示的特定杏仁核基底外侧环路则与小鼠的消极和积极情绪归因有关。我们将基于 CTB 和狂犬病的追踪与体内外神经元活动测量相结合,证明了在抑郁状态下,特定 BLA 回路的活动紊乱支持了负价偏差。长期服用 CORT 会导致优先参与正向价值编码的 BLA 至 NAc 神经元的招募减少,而优先参与负向价值编码的 BLA 至 CEA 神经元的招募增加。重要的是,BLA-to-NAc 神经元的化学超激活抑制了这种功能障碍。此外,BLA 活动的改变与来自丘脑室旁核的持久突触前连接变化相关,而最近的研究表明,丘脑室旁核在杏仁核中协调着价值分配。总之,我们的研究结果表明,特定的BLA回路改变可能会支持抑郁状态下的负偏向,并为转化研究提供了新的途径,以了解抑郁的内在机制和治疗效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Disrupted basolateral amygdala circuits supports negative valence bias in depressive states.

Negative bias is an essential characteristic of depressive episodes leading patients to attribute more negative valence to environmental cues. This negative bias affects all levels of information processing including emotional response, attention and memory, leading to the development and maintenance of depressive symptoms. In this context, pleasant stimuli become less attractive and unpleasant ones more aversive, yet the related neural circuits underlying this bias remain largely unknown. By studying a mice model for depression chronically receiving corticosterone (CORT), we showed a negative bias in valence attribution to olfactory stimuli that responds to antidepressant drug. This result paralleled the alterations in odor value assignment we observed in bipolar depressed patients. Given the crucial role of amygdala in valence coding and its strong link with depression, we hypothesized that basolateral amygdala (BLA) circuits alterations might support negative shift associated with depressive states. Contrary to humans, where limits in spatial resolution of imaging tools impair easy amygdala segmentation, recently unravelled specific BLA circuits implicated in negative and positive valence attribution could be studied in mice. Combining CTB and rabies-based tracing with ex vivo measurements of neuronal activity, we demonstrated that negative valence bias is supported by disrupted activity of specific BLA circuits during depressive states. Chronic CORT administration induced decreased recruitment of BLA-to-NAc neurons preferentially involved in positive valence encoding, while increasing recruitment of BLA-to-CeA neurons preferentially involved in negative valence encoding. Importantly, this dysfunction was dampened by chemogenetic hyperactivation of BLA-to-NAc neurons. Moreover, altered BLA activity correlated with durable presynaptic connectivity changes coming from the paraventricular nucleus of the thalamus, recently demonstrated as orchestrating valence assignment in the amygdala. Together, our findings suggest that specific BLA circuits alterations might support negative bias in depressive states and provide new avenues for translational research to understand the mechanisms underlying depression and treatment efficacy.

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来源期刊
CiteScore
11.50
自引率
2.90%
发文量
484
审稿时长
23 weeks
期刊介绍: Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.
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