Presynaptic nicotinic receptors: a dynamic and diverse cholinergic filter of striatal dopamine neurotransmission
Presynaptic nicotinic receptors: a dynamic and diverse cholinergic filter of striatal dopamine neurotransmission
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DOI：
10.1038/sj.bjp.0707510
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发表时间：
2008-03-01
影响因子：
7.3
通讯作者：
Cragg, S. J.
中科院分区：
文献类型：
--
作者：
Exley, R.;Cragg, S. J.
尼古丁对中纹状体多巴胺神经元多巴胺传递的影响是其强化特性的核心。然而，直到最近才开始了解突触前烟碱受体（nAChRs）对纹状体内多巴胺能轴突终末的影响。在这里，而不是简单地增强（或抑制）多巴胺的释放，nAChRs执行突触前过滤器的作用，其对多巴胺释放概率的影响取决于多巴胺能神经元以及胆碱能神经元的突触前活动。纹状体中多巴胺能神经元和纹状体胆碱能中间神经元在基底神经节的动机和感觉运动处理中起关键作用。此外，多巴胺和乙酰胆碱对纹状体的影响似乎不能完全理解，如果不了解它们的相互作用。我们将审查强大的过滤nAChRs的纹状体多巴胺释放，并讨论其依赖于多巴胺能和胆碱能神经元的活动。我们还将回顾尼古丁如何通过nAChR脱敏作用促进多巴胺突触对活动的敏感性。这种过滤作用可能提供了一种机制，尼古丁通过这种机制促进多巴胺神经元的爆发活动，促进目标导向行为和强化过程。更一般地说，这表明我们不应该将我们对突触前nAChRs的看法局限于简单地增强神经递质的释放。我们还将总结目前的理解的形式和功能的不同nAChRs据称存在于多巴胺能轴突。更好地了解nAChR的形式和功能是必不可少的，以指导设计的配体与亚型选择性的疗效，改善尼古丁成瘾以及帕金森氏病的治疗干预。
The effects of nicotine on dopamine transmission from mesostriatal dopamine neurons are central to its reinforcing properties. Only recently however, has the influence of presynaptic nicotinic receptors (nAChRs) on dopaminergic axon terminals within striatum begun to be understood. Here, rather than simply enhancing ( or inhibiting) dopamine release, nAChRs perform the role of a presynaptic filter, whose influence on dopamine release probability depends on presynaptic activity in dopaminergic as well as cholinergic neurons. Both mesostriatal dopaminergic neurons and striatal cholinergic interneurons play key roles in motivational and sensorimotor processing by the basal ganglia. Moreover, it appears that the striatal influence of dopamine and ACh cannot be fully appreciated without an understanding of their reciprocal interactions. We will review the powerful filtering by nAChRs of striatal dopamine release and discuss its dependence on activity in dopaminergic and cholinergic neurons. We will also review how nicotine, acting via nAChR desensitization, promotes the sensitivity of dopamine synapses to activity. This filtering action might provide a mechanism through which nicotine promotes how burst activity in dopamine neurons facilitates goal-directed behaviour and reinforcement processing. More generally, it indicates that we should not restrict our view of presynaptic nAChRs to simply enhancing neurotransmitter release. We will also summarize current understanding of the forms and functions of the diverse nAChRs purported to exist on dopaminergic axons. A greater understanding of nAChR form and function is imperative to guide the design of ligands with subtype-selective efficacy for improved therapeutic interventions in nicotine addiction as well as Parkinson's disease.