The number and distribution of AMPA receptor channels containing fast kinetic GluA3 and GluA4 subunits at auditory nerve synapses depend on the target cells.

The number and distribution of AMPA receptor channels containing fast kinetic GluA3 and GluA4 subunits at auditory nerve synapses depend on the target cells.
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DOI:
10.1007/s00429-017-1408-0
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发表时间:
2017-11
影响因子:
3.1
通讯作者:
Shigemoto R
Shigemoto R
中科院分区:
医学3区
文献类型:
--
作者:
Rubio ME;Matsui K;Fukazawa Y;Kamasawa N;Harada H;Itakura M;Molnár E;Abe M;Sakimura K;Shigemoto R

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神经递质受体的亚型、数量、密度和相对于递质释放部位位置的分布是信号传递的关键决定因素。含有GluA3和GluA4亚基的AMPA型离子型谷氨酸受体(AMPAR)主要表达于听觉中继神经元等能够高频放电的神经元亚群中。听神经在耳蜗核的丛状细胞(BCS)和梭形细胞(FCS)两种类型的中继神经元上形成谷氨酸能突触。An-BC和An-Fc突触具有不同的动力学特征;因此,我们研究了GluA3和GluA4亚单位在这些突触中的数量、密度和定位是否通过定量冷冻断裂复制免疫金标记法进行了差异组织。我们发现AMPAR的数量与AN-BC和AN-FC突触的大小呈正相关。两种类型的AN突触都有相似数量的AMPAR;然而,AN-BC突触的AMPAR密度比AN-FC突触高,因为AN-BC突触更小。An-BC突触的GluA3亚基数量和密度较高,而An-Fc突触的GluA4亚基的数量和密度较高。免疫金标记法在突触内的分布表明,AMPAR亚单位,尤其是GluA3,集中在AN-BC突触的中心。在GluA3基因敲除小鼠中没有AMPAR的中心分布,金颗粒沿突触后密度均匀分布。GluA4金标记物在两种突触类型中分布均匀。因此,GluA3和GluA4亚基以靶细胞依赖的方式分布在突触上。本文的在线版本(doi:10.1007/s00429-0171408-0)包含补充材料,授权用户可以使用。
The neurotransmitter receptor subtype, number, density, and distribution relative to the location of transmitter release sites are key determinants of signal transmission. AMPA-type ionotropic glutamate receptors (AMPARs) containing GluA3 and GluA4 subunits are prominently expressed in subsets of neurons capable of firing action potentials at high frequencies, such as auditory relay neurons. The auditory nerve (AN) forms glutamatergic synapses on two types of relay neurons, bushy cells (BCs) and fusiform cells (FCs) of the cochlear nucleus. AN-BC and AN-FC synapses have distinct kinetics; thus, we investigated whether the number, density, and localization of GluA3 and GluA4 subunits in these synapses are differentially organized using quantitative freeze-fracture replica immunogold labeling. We identify a positive correlation between the number of AMPARs and the size of AN-BC and AN-FC synapses. Both types of AN synapses have similar numbers of AMPARs; however, the AN-BC have a higher density of AMPARs than AN-FC synapses, because the AN-BC synapses are smaller. A higher number and density of GluA3 subunits are observed at AN-BC synapses, whereas a higher number and density of GluA4 subunits are observed at AN-FC synapses. The intrasynaptic distribution of immunogold labeling revealed that AMPAR subunits, particularly GluA3, are concentrated at the center of the AN-BC synapses. The central distribution of AMPARs is absent in GluA3-knockout mice, and gold particles are evenly distributed along the postsynaptic density. GluA4 gold labeling was homogenously distributed along both synapse types. Thus, GluA3 and GluA4 subunits are distributed at AN synapses in a target-cell-dependent manner. The online version of this article (doi:10.1007/s00429-017-1408-0) contains supplementary material, which is available to authorized users.
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