Fear Memory Retrieval Is Associated With a Reduction in AMPA Receptor Density at Thalamic to Amygdala Intercalated Cell Synapses.
Fear Memory Retrieval Is Associated With a Reduction in AMPA Receptor Density at Thalamic to Amygdala Intercalated Cell Synapses.
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DOI：
10.3389/fnsyn.2021.634558
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发表时间：
2021
影响因子：
3.7
通讯作者：
Ferraguti F
中科院分区：
文献类型：
--
作者：
Seewald A;Schönherr S;Hörtnagl H;Ehrlich I;Schmuckermair C;Ferraguti F
杏仁核在将情绪意义与环境线索联系起来方面起着至关重要的作用。它的嵌入细胞团（ITC）是紧密的GABA能神经元簇，分布在基底外侧杏仁核复合体周围。不同的ITC集群参与条件性恐惧反应的获得和消退。以前，我们已经表明，恐惧记忆提取减少AMPA/NMDA比率在丘脑传入ITC神经元内的背内侧囊旁簇。在这里，我们调查的分子机制的恐惧介导的减少AMPA/NMDA的比例在这些突触，特别是，是否特定的变化AMPA受体的突触密度的基础上观察到的变化。为此，我们使用了去污剂消化的冷冻断裂复制免疫标记技术（FRIL）的方法，使可视化的空间分布的突触内AMPA受体在高分辨率。使用针对所有AMPA亚基共有的表位产生的抗体检测AMPA受体。为了可视化丘脑输入，我们用视紫红质2-YFP病毒转导后丘脑复合体，其沿沿着轴突顺行运输。利用面匹配复制品，我们证实了突触后元件是ITC神经元，因为它们显著表达μ-阿片受体。通过这种方法，我们发现，在小鼠听觉恐惧条件反射后，恐惧记忆的形成和恢复与AMPA受体密度的显着降低有关，特别是在由后板内丘脑和内侧膝状体核的输入到确定的ITC神经元上形成的脊柱突触处。我们的研究是为数不多的直接关联的AMPA受体运输的调节，以记忆过程中确定的神经元网络，通过显示恐惧记忆诱导的AMPA/NMDA比率减少在丘脑-ITC突触与突触后AMPA受体密度降低。
The amygdala plays a crucial role in attaching emotional significance to environmental cues. Its intercalated cell masses (ITC) are tight clusters of GABAergic neurons, which are distributed around the basolateral amygdala complex. Distinct ITC clusters are involved in the acquisition and extinction of conditioned fear responses. Previously, we have shown that fear memory retrieval reduces the AMPA/NMDA ratio at thalamic afferents to ITC neurons within the dorsal medio-paracapsular cluster. Here, we investigate the molecular mechanisms underlying the fear-mediated reduction in the AMPA/NMDA ratio at these synapses and, in particular, whether specific changes in the synaptic density of AMPA receptors underlie the observed change. To this aim, we used a detergent-digested freeze-fracture replica immunolabeling technique (FRIL) approach that enables to visualize the spatial distribution of intrasynaptic AMPA receptors at high resolution. AMPA receptors were detected using an antibody raised against an epitope common to all AMPA subunits. To visualize thalamic inputs, we virally transduced the posterior thalamic complex with Channelrhodopsin 2-YFP, which is anterogradely transported along axons. Using face-matched replica, we confirmed that the postsynaptic elements were ITC neurons due to their prominent expression of μ-opioid receptors. With this approach, we show that, following auditory fear conditioning in mice, the formation and retrieval of fear memory is linked to a significant reduction in the density of AMPA receptors, particularly at spine synapses formed by inputs of the posterior intralaminar thalamic and medial geniculate nuclei onto identified ITC neurons. Our study is one of the few that has directly linked the regulation of AMPA receptor trafficking to memory processes in identified neuronal networks, by showing that fear-memory induced reduction in AMPA/NMDA ratio at thalamic-ITC synapses is associated with a reduced postsynaptic AMPA receptor density.
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DOI：
10.1101/lm.044131.116
发表时间：
2017-09
期刊：
Learning & memory (Cold Spring Harbor, N.Y.)
影响因子：
--
作者：
Ferrara NC;Cullen PK;Pullins SP;Rotondo EK;Helmstetter FJ
通讯作者：
Helmstetter FJ
影响因子：
64.8
作者：
Ciocchi, Stephane;Herry, Cyril;Luethi, Andreas
通讯作者：
Luethi, Andreas
影响因子：
16.2
作者：
Duvarci S;Pare D
通讯作者：
Pare D
影响因子：
2.5
作者：
Dong, Yu-Lin;Fukazawa, Yugo;Shigemoto, Ryuichi
通讯作者：
Shigemoto, Ryuichi
影响因子：
16.2
作者：
Asede, Douglas;Bosch, Daniel;Ehrlich, Ingrid
通讯作者：
Ehrlich, Ingrid