Alpha7 nicotinic acetylcholine receptors occur at postsynaptic densities of AMPA receptor-positive and -negative excitatory synapses in rat sensory cortex.
Alpha7 nicotinic acetylcholine receptors occur at postsynaptic densities of AMPA receptor-positive and -negative excitatory synapses in rat sensory cortex.
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发表时间：
2002
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通讯作者：
Robert B. Levy;C. Aoki
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作者：
Robert B. Levy;C. Aoki
NMDA受体（NMDAR）的激活需要同时发生的膜去极化，而缺乏AMPA受体（AMPAR）的突触在缺乏另一种膜去极化来源的情况下通常被认为是“沉默的”。在出生后的第二周，NMDA电流可以通过激活α 7烟碱乙酰胆碱受体（α 7 nAChR）在大鼠听觉皮层增强。电生理结果支持在这些突触的α 7nAChR主要突触前的作用。然而，免疫细胞化学证据表明，α 7 nAChR在海马和新皮质中谷氨酸能突触的突触后位点普遍存在，以及新皮质和海马中突触后尼古丁电流的新电生理证据，沿着出现，促使人们猜测α 7 nAChR允许在缺乏AMPAR的突触处突触后激活NMDAR。在这里，我们使用双重免疫标记和电子显微镜检查分布的α 7 nAChR相对于AMPAR（GluR1，GluR2和GluR3亚基组合）在兴奋性突触在体感皮层的成年和1周龄大鼠。α 7nAChR离散发生在两个年龄组的所有皮质层的大部分厚突触后密度。AMPAR免疫反应也可检测到在大多数突触，其分布是独立的α 7 nAChR。在这两个年龄组中，大约四分之一的不对称突触是alpha7nAChR阳性和AMPAR阴性。突触后α 7nAChR标记密度的变异性在出生后第7天（PD）比在成年期更大，PD 7 neurological包含一个子集的小AMPA受体阴性突触与高密度的α 7nAChR免疫反应性。这些观察结果支持了这样的观点，即乙酰胆碱受体可以帮助激活突触能突触，并与AMPA受体一起介导整个生命过程中的突触后兴奋。
NMDA receptor (NMDAR) activation requires concurrent membrane depolarization, and glutamatergic synapses lacking AMPA receptors (AMPARs) are often considered "silent" in the absence of another source of membrane depolarization. During the second postnatal week, NMDA currents can be enhanced in rat auditory cortex through activation of the alpha7 nicotinic acetylcholine receptor (alpha7nAChR). Electrophysiological results support a mainly presynaptic role for alpha7nAChR at these synapses. However, immunocytochemical evidence that alpha7nAChR is prevalent at postsynaptic sites of glutamatergic synapses in hippocampus and neocortex, along with emerging electrophysiological evidence for postsynaptic nicotinic currents in neocortex and hippocampus, has prompted speculation that alpha7nAChR allows for activation of NMDAR postsynaptically at synapses lacking AMPAR. Here we used dual immunolabeling and electron microscopy to examine the distribution of alpha7nAChR relative to AMPAR (GluR1, GluR2, and GluR3 subunits combined) at excitatory synapses in somatosensory cortex of adult and 1-week-old rats. alpha7nAChR occurred discretely over most of the thick postsynaptic densities in all cortical layers of both age groups. AMPAR immunoreactivity was also detectable at most synapses; its distribution was independent of that of alpha7nAChR. In both age groups, approximately one-quarter of asymmetrical synapses were alpha7nAChR positive and AMPAR negative. The variability of postsynaptic alpha7nAChR labeling density was greater at postnatal day (PD) 7 than in adulthood, and PD 7 neuropil contained a subset of small AMPA receptor-negative synapses with a high density of alpha7nAChR immunoreactivity. These observations support the idea that acetylcholine receptors can aid in activating glutamatergic synapses and work together with AMPA receptors to mediate postsynaptic excitation throughout life.