Zoli Michele, Pistillo Francesco, Gotti Cecilia
Department of Biomedical, Metabolic and Neural Sciences, Section of Physiology and Neurosciences, University of Modena and Reggio Emilia, Modena, Italy.
CNR, Neuroscience Institute-Milano, Biometra Institute University of Milan, Milan, Italy.
Neuropharmacology. 2015 Sep;96(Pt B):302-11. doi: 10.1016/j.neuropharm.2014.11.003. Epub 2014 Nov 25.
Neuronal nicotinic acetylcholine receptors (nAChRs) are a heterogeneous family of pentameric ligand-gated cation channels that are expressed throughout the brain and involved in a wide range of physiological and pathophysiological processes. The nAChR subtypes share a common basic structure, but their biophysical and pharmacological properties depend on their subunit composition, which is therefore central to understanding their function in the nervous system and discovering new subtype selective drugs. The development of new technologies and the generation of mice carrying deletions or the expression of gain-of-function nAChR subunits, or GFP-tagged receptor genes has allowed the in vivo identification of complex subtypes and to study the role of individual subtypes in specific cells and complex neurobiological systems but much less is known about which native nAChR subtypes are involved in specific physiological functions and pathophysiological conditions in human brain. We briefly review some recent findings concerning the structure and function of native nAChRs, focussing on the subtypes identified in the rodent habenulo-interpeduncular pathway, a pathway involved in nicotine reinforcement and withdrawal. We also discuss recent findings concerning the expression of native subtypes in primate brain. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'.
神经元烟碱型乙酰胆碱受体（nAChRs）是一个由五聚体配体门控阳离子通道组成的异质家族，在整个大脑中表达，并参与广泛的生理和病理生理过程。nAChR亚型具有共同的基本结构，但其生物物理和药理学特性取决于其亚基组成，因此这对于理解它们在神经系统中的功能以及发现新的亚型选择性药物至关重要。新技术的发展以及携带nAChR亚基缺失或功能增强表达的小鼠的产生，或带有绿色荧光蛋白（GFP）标记的受体基因，使得能够在体内鉴定复杂的亚型，并研究单个亚型在特定细胞和复杂神经生物学系统中的作用，但对于哪些天然nAChR亚型参与人类大脑的特定生理功能和病理生理状况，人们所知甚少。我们简要回顾了一些关于天然nAChRs结构和功能的最新发现，重点关注在啮齿动物缰核-脚间核通路中鉴定出的亚型，该通路参与尼古丁强化和戒断过程。我们还讨论了关于天然亚型在灵长类大脑中表达的最新发现。本文是名为“烟碱型乙酰胆碱受体：从分子生物学到认知”的特刊的一部分。
