Hippocampal GABAergic Synapses Possess the Molecular Machinery for Retrograde Nitric Oxide Signaling
Hippocampal GABAergic Synapses Possess the Molecular Machinery for Retrograde Nitric Oxide Signaling
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DOI：
10.1523/jneurosci.1912-07.2007
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发表时间：
2007-07
期刊：
影响因子：
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通讯作者：
Eszter Szabadits;C. Cserép;Anikó Ludányi;I. Katona;J. Gracia-Llanes;T. Freund;G. Nyiri
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文献类型：
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作者：
Eszter Szabadits;C. Cserép;Anikó Ludányi;I. Katona;J. Gracia-Llanes;T. Freund;G. Nyiri
一氧化氮（NO）作为谷氨酸能突触的逆行信使，在突触可塑性中起着重要作用。在这里，我们描述了在小鼠和大鼠的海马锥体细胞中，神经元一氧化氮合酶（nNOS）也与终止于其躯体、树突和轴突初始段的gaba能对称突触的突触后活跃区有关。NO受体一氧化氮敏感鸟苷环化酶（NOsGC）在大脑中以α1β1和α2β1两种功能亚基组成存在。β1亚基在海马锥体细胞和中间神经元中均有表达。利用免疫组织化学和原位杂交方法，我们发现α1亚基仅在中间神经元中检测到，而中间神经元中β1亚基也始终呈阳性；然而，锥体细胞仅标记β1和α2亚基。通过双免疫荧光染色，我们还发现大多数胆囊收缩素和小球蛋白阳性，少量生长抑素和nnos阳性的中间神经元α1亚基阳性。我们还发现α1亚基存在于小白蛋白和胆囊收缩素阳性的中间神经元终末，这些终末在体细胞、树突或轴突初始段上建立突触。结果表明，由α1β1亚基组成的NOsGC在不同类型的中间神经元中选择性表达，并存在于其突触前gaba能末端，可能作为nNOS在同一突触中突触后产生NO的受体。
Nitric oxide (NO) plays an important role in synaptic plasticity as a retrograde messenger at glutamatergic synapses. Here we describe that, in hippocampal pyramidal cells, neuronal nitric oxide synthase (nNOS) is also associated with the postsynaptic active zones of GABAergic symmetrical synapses terminating on their somata, dendrites, and axon initial segments in both mice and rats. The NO receptor nitric oxide-sensitive guanylyl cyclase (NOsGC) is present in the brain in two functional subunit compositions: α1β1 and α2β1. The β1 subunit is expressed in both pyramidal cells and interneurons in the hippocampus. Using immunohistochemistry and in situ hybridization methods, we describe that the α1 subunit is detectable only in interneurons, which are always positive for β1 subunit as well; however, pyramidal cells are labeled only for β1 and α2 subunits. With double-immunofluorescent staining, we also found that most cholecystokinin- and parvalbumin-positive and smaller proportion of the somatostatin- and nNOS-positive interneurons are α1 subunit positive. We also found that the α1 subunit is present in parvalbumin- and cholecystokinin-positive interneuron terminals that establish synapses on somata, dendrites, or axon initial segments. Our results demonstrate that NOsGC, composed of α1β1 subunits, is selectively expressed in different types of interneurons and is present in their presynaptic GABAergic terminals, in which it may serve as a receptor for NO produced postsynaptically by nNOS in the very same synapse.