Preferential Localization of Muscarinic M1 Receptor on Dendritic Shaft and Spine of Cortical Pyramidal Cells and Its Anatomical Evidence for Volume Transmission
Preferential Localization of Muscarinic M1 Receptor on Dendritic Shaft and Spine of Cortical Pyramidal Cells and Its Anatomical Evidence for Volume Transmission
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DOI：
10.1523/jneurosci.5719-09.2010
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发表时间：
2010-03
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影响因子：
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通讯作者：
Miwako Yamasaki;M. Matsui;Masahiko Watanabe
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作者：
Miwako Yamasaki;M. Matsui;Masahiko Watanabe
乙酰胆碱（Acetylcholine，ACh）对大脑的高级功能起着重要的作用，包括唤醒、注意力和认知。这些作用主要由毒蕈碱乙酰胆碱受体（mAChR）介导。然而，它仍然是不确定的ACh-mAChR信号的模式是突触，所谓的“有线”，传输介导的ACh释放到突触间隙，或非突触，所谓的“体积”，传输环境ACh。为了解决这个问题，我们研究了细胞和亚细胞分布的M1，最主要的mAChR亚型在大脑皮层和海马，并追求其与胆碱能静脉曲张在这些地区的成年小鼠的解剖关系。M1在海马锥体神经元中高表达，而在各种GABA能中间神经元亚型中低表达或检测不到。M1主要分布在锥体细胞、树突和棘的突触外膜上。胆碱能静脉曲张常与锥体细胞、树突和突触直接接触。然而，在这样的接触网站，突触样专业化是罕见的，并没有特别的积累，发现在周围的M1和突触前活动区蛋白巴松接触网站。这些功能与AMPA受体GluA 2和代谢型受体mGluR 5分别被募集到突触或突触周膜的AMPA能系统形成对比，并且巴松管在突触前末梢中高度积累。这些结果表明，M1是如此定位，以感知周围ACh释放的胆碱能静脉曲张在可变的距离，并提高突触的功效和兴奋性的锥体细胞。这些分子解剖学的安排将提供证据的体积传输，至少在M1介导的皮质胆碱能信号。
Acetylcholine (ACh) plays important roles for higher brain functions, including arousal, attention, and cognition. These effects are mediated largely by muscarinic acetylcholine receptors (mAChRs). However, it remains inconclusive whether the mode of ACh-mAChR signaling is synaptic, so-called “wired,” transmission mediated by ACh released into the synaptic cleft, or nonsynaptic, so-called “volume,” transmission by ambient ACh. To address this issue, we examined cellular and subcellular distribution of M1, the most predominant mAChR subtype in the cerebral cortex and hippocampus, and pursued its anatomical relationship with cholinergic varicosities in these regions of adult mice. M1 was highly expressed in glutamatergic pyramidal neurons, whereas it was low or undetectable in various GABAergic interneuron subtypes. M1 was preferentially distributed on the extrasynaptic membrane of pyramidal cell dendrites and spines. Cholinergic varicosities often made direct contact to pyramidal cell dendrites and synapses. At such contact sites, however, synapse-like specialization was infrequent, and no particular accumulation was found at around contact sites for both M1 and presynpatic active zone protein Bassoon. These features contrasted with those of the glutamatergic system, in which AMPA receptor GluA2 and metabotropic receptor mGluR5 were recruited to the synaptic or perisynaptic membrane, respectively, and Bassoon was highly accumulated in the presynaptic terminals. These results suggest that M1 is so positioned to sense ambient ACh released from cholinergic varicosities at variable distances, and to enhance the synaptic efficacy and excitability of pyramidal cells. These molecular–anatomical arrangements will provide the evidence for volume transmission, at least in M1-mediated cortical cholinergic signaling.