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阿立新受体拮抗剂促进情境性恐惧消退与特定杏仁核细胞亚群的激活有关。

Facilitation of Contextual Fear Extinction by Orexin-1 Receptor Antagonism Is Associated with the Activation of Specific Amygdala Cell Subpopulations.

机构信息

Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain (Drs Flores, Maldonado, and Berrendero); INSERM, Neurocentre Magendie, Bordeaux, France (Dr Herry); University Bordeaux, Neurocentre Magendie, Bordeaux, France (Dr Herry); Faculty of Experimental Sciences, Universidad Francisco de Vitoria, Madrid, Spain (Dr Berrendero).

出版信息

Int J Neuropsychopharmacol. 2017 Aug 1;20(8):654-659. doi: 10.1093/ijnp/pyx029.

DOI:10.1093/ijnp/pyx029
PMID:28453642
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5570099/
Abstract

BACKGROUND

Orexins are hypothalamic neuropeptides recently involved in the regulation of emotional memory. The basolateral amygdala, an area orchestrating fear memory processes, appears to be modulated by orexin transmission during fear extinction. However, the neuronal types within the basolateral amygdala involved in this modulation remain to be elucidated.

METHODS

We used retrograde tracing combined with immunofluorescence techniques in mice to identify basolateral amygdala projection neurons and cell subpopulations in this brain region influenced by orexin transmission during contextual fear extinction consolidation.

RESULTS

Treatment with the orexin-1 receptor antagonist SB334867 increased the activity of basolateral amygdala neurons projecting to infralimbic medial prefrontal cortex during fear extinction. GABAergic interneurons expressing calbindin, but not parvalbumin, were also activated by orexin-1 receptor antagonism in the basolateral amygdala.

CONCLUSIONS

These data identify neuronal circuits and cell populations of the amygdala associated with the facilitation of fear extinction consolidation induced by the orexin-1 receptor antagonist SB334867.

摘要

背景

食欲素是最近参与调节情绪记忆的下丘脑神经肽。外侧杏仁核是协调恐惧记忆过程的区域,在恐惧消退期间,似乎受到食欲素传递的调节。然而,在这种调节中涉及的外侧杏仁核神经元类型仍有待阐明。

方法

我们使用逆行示踪结合免疫荧光技术在小鼠中鉴定外侧杏仁核投射神经元和细胞亚群,这些神经元和细胞亚群在上下文恐惧消退巩固期间受到食欲素传递的影响。

结果

使用食欲素-1 受体拮抗剂 SB334867 治疗可增加投射到边缘下前额叶皮质的外侧杏仁核神经元在恐惧消退期间的活性。外侧杏仁核中表达钙结合蛋白的 GABA 能中间神经元,而不是表达钙结合蛋白的中间神经元,也被食欲素-1 受体拮抗剂激活。

结论

这些数据确定了与食欲素-1 受体拮抗剂 SB334867 诱导的恐惧消退巩固促进相关的杏仁核神经元回路和细胞群体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed45/5570099/415d6d41543c/pyx02902.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed45/5570099/7d32b6aa0d41/pyx02901.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed45/5570099/415d6d41543c/pyx02902.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed45/5570099/7d32b6aa0d41/pyx02901.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed45/5570099/415d6d41543c/pyx02902.jpg

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Orexins and fear: implications for the treatment of anxiety disorders.
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Fear attenuation collaborations to optimize translation.恐惧衰减合作以优化翻译。
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Hypocretin (Orexin) Replacement Therapies.下丘脑泌素(食欲素)替代疗法。
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