Nicotinic acetylcholine receptor-mediated GABAergic inputs to cholinergic interneurons in the striosomes and the matrix compartments of the mouse striatum
Nicotinic acetylcholine receptor-mediated GABAergic inputs to cholinergic interneurons in the striosomes and the matrix compartments of the mouse striatum
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烟碱乙酰胆碱受体介导的 GABA 能输入至小鼠纹状体纹状体和基质区室中的胆碱能中间神经元
DOI：
10.1016/j.neuropharm.2016.01.029
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Miura M
中科院分区：
文献类型：
--
作者：
Inoue R;Suzuki T;Nishimura K;Miura M
纹状体由两个神经化学上不同的区室组成：纹状体（或斑块）和纹状体外基质。虽然纹状体神经元强烈受内在胆碱能中间神经元的支配，但乙酰胆碱酯酶在基质中比在纹状体中表达更丰富。目前，很少有人知道不同的胆碱能功能的纹状体区室。在这项研究中，我们研究了γ-氨基丁酸（GABA能）的输入胆碱能中间神经元在两个车厢。我们发现烟碱受体介导的GABA能反应在基质中比在纹状体中更频繁地被诱发。此外，胆碱能神经元的单个动作电位诱导尼古丁受体介导的GABA能输入至胆碱能神经元本身，这表明相互联系塑造了胆碱能神经元的时间放电模式。连续应用乙酰胆碱或乙酰胆碱酯酶抑制剂艾司氯胺酮可减弱烟碱受体介导的GABA能反应，并可通过去甲酰基氟曲溴（一种含烟碱受体的α4β2亚基的正变构调节剂）增强。这些结果表明，烟碱对GABA能反应的影响是不均匀的，尽管大量和连续的胆碱能神经支配。据报道，纹状体和基质中的神经元的差异激活产生称为刻板的重复行为。作用于α4β2烟碱受体的药物可能为调节室间的不平衡活动提供潜在的工具。
The striatum consists of two neurochemically distinct compartments: the striosomes (or patches) and the extrastriosomal matrix. Although striatal neurons are strongly innervated by intrinsic cholinergic interneurons, acetylcholinesterase is expressed more abundantly in the matrix than in the striosomes. At present, little is known about the different cholinergic functions of the striatal compartments. In this study, we examined gamma-aminobutyric acidergic (GABAergic) inputs to cholinergic interneurons in both compartments. We found that nicotinic receptor-mediated GABAergic responses were evoked more frequently in the matrix than in the striosomes. Furthermore, a single action potential of cholinergic neurons induced nicotinic receptor-mediated GABAergic inputs to the cholinergic neurons themselves, suggesting mutual connections that shape the temporal firing pattern of cholinergic neurons. The nicotinic receptor-mediated GABAergic responses were attenuated by continuous application of acetylcholine or the acetylcholinesterase inhibitor eserine and were enhanced by desformylflustrabromine, a positive allosteric modulator of the α4β2 subunit containing a nicotinic receptor. These results suggest that the nicotinic impact on the GABAergic responses are not uniform despite the massive and continuous cholinergic innervation. It has been reported that differential activation of neurons in the striosomes and the matrix produce a repetitive behavior called stereotypy. Drugs acting on α4β2 nicotinic receptors might provide potential tools for moderating the imbalanced activities between the compartments.