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巴氯芬在杏仁中央核发挥作用,减少突触传递,并损害情境恐惧条件反射。

Baclofen acts in the central amygdala to reduce synaptic transmission and impair context fear conditioning.

机构信息

School of Biomedical Sciences, Charles Sturt University, Orange, NSW, 2800, Australia.

School of Medicine, University of Tasmania, Hobart, TAS, 7000, Australia.

出版信息

Sci Rep. 2018 Jul 2;8(1):9908. doi: 10.1038/s41598-018-28321-0.

DOI:10.1038/s41598-018-28321-0
PMID:29967489
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6028433/
Abstract

The two main sub-divisions of the Central amygdala (CeA), the lateral-capsular (CeA-LC) and the medial (CeA-M), contain extensive networks of inhibitory interneurons. We have previously shown that activation of GABA-receptors reduces excitatory transmission between axons of the pontine parabrachial nucleus and neurons of the CeA-LC by inhibiting glutamate release from presynaptic terminals. Here we have characterised GABA-receptor activation on other excitatory and inhibitory projections within the CeA. Using whole-cell, patch-clamp recordings, we found that the GABA-receptor agonist baclofen significantly reduced excitatory and inhibitory transmission from all tested inputs into the CeA-LC and CeA-M. In all but one of the inputs, reductions in transmission were accompanied by an increase in paired pulse ratio, indicating that presynaptic GABA-receptors acted to reduce the release probability of synaptic vesicles. To examine the impact of GABA-receptors in the CeA on contextual fear-conditioning, we infused baclofen into the CeA immediately prior to training. Compared to vehicle-infused rats, baclofen-infused rats displayed significantly less freezing both during the final stages of the training period and at test 24 hours later. The results of this study demonstrate that, by suppressing excitatory and inhibitory transmission, activation of presynaptic GABA-receptors in the CeA inhibits the development of context conditioned fear.

摘要

杏仁中央核(CeA)的两个主要亚区,即外侧-胶囊(CeA-LC)和内侧(CeA-M),包含广泛的抑制性中间神经元网络。我们之前已经表明,通过抑制来自突触前末梢的谷氨酸释放,GABA 受体的激活可减少桥脑臂旁核轴突与 CeA-LC 神经元之间的兴奋性传递。在这里,我们描述了 CeA 内其他兴奋性和抑制性投射中的 GABA 受体激活。使用全细胞膜片钳记录,我们发现 GABA 受体激动剂巴氯芬可显著降低所有测试传入 CeA-LC 和 CeA-M 的兴奋性和抑制性传递。在除一个输入之外的所有输入中,传递减少伴随着成对脉冲比的增加,表明突触前 GABA 受体可降低突触小泡释放的概率。为了研究 CeA 中的 GABA 受体对情境性恐惧条件反射的影响,我们在训练前立即将巴氯芬注入 CeA。与载体输注大鼠相比,巴氯芬输注大鼠在训练的最后阶段和 24 小时后的测试中表现出明显较少的冻结。这项研究的结果表明,通过抑制兴奋性和抑制性传递,CeA 中的突触前 GABA 受体的激活抑制了情境条件性恐惧的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b77/6028433/89500075e833/41598_2018_28321_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b77/6028433/17a559e9a8c0/41598_2018_28321_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b77/6028433/66558390b2ec/41598_2018_28321_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b77/6028433/99935072b6fe/41598_2018_28321_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b77/6028433/b2ed9c7af4fb/41598_2018_28321_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b77/6028433/c982f81ae961/41598_2018_28321_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b77/6028433/fd670729e916/41598_2018_28321_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b77/6028433/89500075e833/41598_2018_28321_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b77/6028433/17a559e9a8c0/41598_2018_28321_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b77/6028433/66558390b2ec/41598_2018_28321_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b77/6028433/99935072b6fe/41598_2018_28321_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b77/6028433/b2ed9c7af4fb/41598_2018_28321_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b77/6028433/c982f81ae961/41598_2018_28321_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b77/6028433/fd670729e916/41598_2018_28321_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b77/6028433/89500075e833/41598_2018_28321_Fig7_HTML.jpg

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