Interplay of β2*nicotinic receptors and dopamine pathways in the control of spontaneous locomotion
Interplay of β2*nicotinic receptors and dopamine pathways in the control of spontaneous locomotion
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DOI：
10.1073/pnas.0807635105
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发表时间：
2008-10-14
影响因子：
11.1
通讯作者：
Maskos, Uwe
中科院分区：
文献类型：
--
作者：
Avale, Maria Elena;Faure, Philippe;Maskos, Uwe
乙酰胆碱（ACh）是一种已知的多巴胺能（DAergic）神经元活性调节剂，通过刺激烟碱乙酰胆碱受体（nAChRs）。然而，参与da介导的运动的nachr的亚基组成和具体位置在体内仍有待确定。缺乏nAChRs β 2亚基（β 2KO）的小鼠在开阔视野中表现出惊人的过度活跃，这表明DA神经传递不平衡。在这里，我们在β 2KO小鼠的黑质部致密（SNpc）或腹侧被盖区（VTA）中对功能性β 2*-nAChRs进行了选择性基因拯救。SNpc修复的小鼠在熟悉和不熟悉的环境中均表现出正常的运动活动，而VTA修复仅恢复了探索行为。这些数据证明了黑质纹状体和中边缘β 2*- nachr在调节独特的运动功能方面的分离。此外，RNA干扰SNpc中β 2亚基的定点敲低导致野生型小鼠过度活跃。这些发现强调了nachr在DA控制自发运动中的重要相互作用。
Acetylcholine (ACh) is a known modulator of the activity of dopaminergic (DAergic) neurons through the stimulation of nicotinic ACh receptors (nAChRs). Yet, the subunit composition and specific location of nAChRs involved in DA-mediated locomotion remain to be established in vivo. Mice lacking the beta 2 subunit of nAChRs (beta 2KO) display striking hyperactivity in the open field, which suggests an imbalance in DA neurotransmission. Here, we performed the selective gene rescue of functional beta 2*-nAChRs in either the substantia nigra pars compacta (SNpc) or the ventral tegmental area (VTA) of beta 2KO mice. SNpc rescued mice displayed normalization of locomotor activity, both in familiar and unfamiliar environments, whereas restoration in the VTA only rescued exploratory behavior. These data demonstrate the dissociation between nigrostriatal and mesolimbic beta 2*-nAChRs in regulating unique locomotor functions. In addition, the site-directed knockdown of the beta 2 subunit in the SNpc by RNA interference caused hyperactivity in wild-type mice. These findings highlight the crucial interplay of nAChRs over the DA control of spontaneous locomotion.