Ultrastructural distribution of the α7 nicotinic acetylcholine receptor subunit in rat hippocampus

Ultrastructural distribution of the α7 nicotinic acetylcholine receptor subunit in rat hippocampus
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DOI:
10.1523/jneurosci.21-20-07993.2001
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发表时间:
2001-10-15
影响因子:
5.3
通讯作者:
Fine, A
Fine, A
中科院分区:
医学1区
文献类型:
--
作者:
Fabian-Fine, R;Skehel, P;Fine, A

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乙酰胆碱(ACh)是哺乳动物大脑中一种重要的神经递质;它与觉醒、学习和其他认知功能有关。最近的研究表明,除了毒蕈碱受体的既定作用外,烟碱受体也参与了这些胆碱能作用。在胆碱能参与学习和记忆的海马体中,alpha7烟碱乙酰胆碱受体亚基(alpha7 nachr)高度表达,但其精确的超微结构定位尚未确定。本文描述了大鼠CA1区辐射层连续超薄切片免疫金标记的结果。使用抗α - 7 nAChR免疫标记和α -bungarotoxin结合,我们发现α - 7 nAChR存在于CA1辐射层的几乎所有突触中,并且在突触前和突触后都存在免疫标记。形态学观察和双重免疫标记表明,gaba能突触和谷氨酸能突触都携带α 7 nachr,其密度接近CA1辐射层中谷氨酸受体的密度。突触后,alpha7 nachr通常分布在突触周围环的树突棘上。在突触后细胞质中,免疫标记与脊柱装置和其他膜性结构相关,表明alpha7 nachr可能经历动态调节,插入突触并随后内化。alpha7 nachr在海马突触中广泛而大量的表达,与在介导和/或调节突触传递、可塑性和神经退行性方面的重要作用相一致。
Acetylcholine (ACh) is an important neurotransmitter in the mammalian brain; it is implicated in arousal, learning, and other cognitive functions. Recent studies indicate that nicotinic receptors contribute to these cholinergic effects, in addition to the established role of muscarinic receptors. In the hippocampus, where cholinergic involvement in learning and memory is particularly well documented, alpha7 nicotinic acetylcholine receptor subunits (alpha7 nAChRs) are highly expressed, but their precise ultrastructural localization has not been determined. Here, we describe the results of immunogold labeling of serial ultrathin sections through stratum radiatum of area CA1 in the rat. Using both anti-alpha7 nAChR immunolabeling and alpha -bungarotoxin binding, we find that alpha7 nAChRs are present at nearly all synapses in CA1 stratum radiatum, with immunolabeling present at both presynaptic and postsynaptic elements. Morphological considerations and double immunolabeling indicate that GABAergic as well as glutamatergic synapses bear alpha7 nAChRs, at densities approaching those observed for glutamate receptors in CA1 stratum radiatum. Postsynaptically, alpha7 nAChRs often are distributed at dendritic spines in a perisynaptic annulus. In the postsynaptic cytoplasm, immunolabeling is associated with spine apparatus and other membranous structures, suggesting that alpha7 nAChRs may undergo dynamic regulation, with insertion into the synapse and subsequent internalization. The widespread and substantial expression of alpha7 nAChRs at synapses in the hippocampus is consistent with an important role in mediating and/or modulating synaptic transmission, plasticity, and neurodegeneration.