Gotti Cecilia, Moretti Milena, Zanardi Alessio, Gaimarri Annalisa, Champtiaux Nicolas, Changeux Jean-Pierre, Whiteaker Paul, Marks Michael J, Clementi Francesco, Zoli Michele
CNR, Institute of Neuroscience, Section of Cellular and Molecular Pharmacology Center, Department of Medical Pharmacology, University of Milan, Italy.
Mol Pharmacol. 2005 Oct;68(4):1162-71. doi: 10.1124/mol.105.015925. Epub 2005 Jul 27.
The activation of neuronal nicotinic acetylcholine receptors (nAChRs) has been implicated in the activity-dependent development and plasticity of retina and the refinement of retinal projections. Pharmacological and functional studies have also indicated that different presynaptic nAChRs can have a modulatory function in retinotectal synapses. We biochemically and pharmacologically identified the multiple nAChR subtypes expressed on retinal afferents of the superior colliculus (SC) and lateral geniculate nucleus (LGN). We found that the alpha6beta2() and alpha4(nonalpha6)beta2() nAChRs are the major receptor populations expressed in both SC and LGN. In addition, the LGN contains two minor populations of alpha2alpha6beta2() and alpha3beta2() subtypes, whereas the SC contains a relatively large population of a new native subtype, the alpha3beta2(alpha5/beta3) nAChR. This subtype binds the alpha-conotoxin MII with an affinity 50 times lower than that of the native alpha6beta2() subtype. Studies of tissues obtained from eye-enucleated animals allowed the identification of nAChRs expressed by retinal afferents: in SC alpha6beta2(), alpha4alpha6beta2(), and alpha3beta2() (approximately 45, 35, and 20%, respectively), in LGN, alpha4alpha6beta2(), alpha6beta2(), alpha4beta2(), alpha2alpha6beta2(), and alpha3beta2() (approximately 40, 30, 20, 5, and 5%, respectively). In both regions, more than 50% of nAChRs were not expressed by retinal afferents and belonged to the alpha4beta2() (90%) or alpha4alpha5beta2(*) (10%) subtypes. Moreover, studies of the SC tissues obtained from wild-type and alpha4, alpha6, and beta3 knockout mice confirmed and extended the data obtained in rat tissue and allowed a comprehensive dissection of the composition of nAChR subtypes present in this retinorecipient area.
神经元烟碱型乙酰胆碱受体（nAChRs）的激活与视网膜活动依赖性发育和可塑性以及视网膜投射的精细化有关。药理学和功能研究还表明，不同的突触前nAChRs在视网膜顶盖突触中可具有调节功能。我们通过生物化学和药理学方法鉴定了在上丘（SC）和外侧膝状体核（LGN）的视网膜传入纤维上表达的多种nAChR亚型。我们发现α6β2（）和α4（非α6）β2（）nAChRs是在SC和LGN中表达的主要受体群体。此外，LGN含有少量的α2α6β2（）和α3β2（）亚型群体，而SC含有相对大量的一种新的天然亚型，即α3β2（α5/β3）nAChR。该亚型与α-芋螺毒素MII的结合亲和力比天然α6β2（）亚型低50倍。对取自摘除眼球动物的组织进行研究，有助于鉴定视网膜传入纤维表达的nAChRs：在SC中，α6β2（）、α4α6β2（）和α3β2（）（分别约为45%、35%和20%），在LGN中，α4α6β2（）、α6β2（）、α4β2（）、α2α6β2（）和α3β2（）（分别约为40%、30%、20%、5%和5%）。在这两个区域中，超过50%的nAChRs并非由视网膜传入纤维表达，而是属于α4β2（）（90%）或α4α5β2（*）（10%）亚型。此外，对取自野生型以及α4、α6和β3基因敲除小鼠的SC组织进行研究，证实并扩展了在大鼠组织中获得的数据，从而能够全面剖析该视网膜接受区中存在的nAChR亚型的组成。
