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首页> 外文期刊>The Cerebellum >Cerebellar Nicotinic Cholinergic Receptors are Intrinsic to the Cerebellum: Implications for Diverse Functional Roles
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Cerebellar Nicotinic Cholinergic Receptors are Intrinsic to the Cerebellum: Implications for Diverse Functional Roles

机译：小脑烟碱胆碱能受体是小脑固有的：对多种功能作用的影响。

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摘要

Although recent studies have delineated the specific nicotinic subtypes present in the mammalian cerebellum, very little is known about their location or function within the cerebellum. This is of increased interest since nicotinic receptors (nAChRs) in the cerebellum have recently been implicated in the pathology of autism spectrum disorders. To begin to better understand the roles of these heteromeric nAChRs in the cerebellar circuitry and their therapeutic potential as targets for drug development, we used various chemical and stereotaxic lesion models in conjunction with slice electrophysiology to examine how specific heteromeric nAChR subtypes may influence the surrounding cerebellar circuitry. Using subunit-specific immunoprecipitation of radiolabeled nAChRs in the cerebella following N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride, p-chloroamphetamine, and pendunculotomy lesions, we show that most, if not all, cerebellar nicotinic receptors are present in cells within the cerebellum itself and not in extracerebellar afferents. Furthermore, we demonstrate that the β4-containing, but not the β2-containing, nAChRs intrinsic to the cerebellum can regulate inhibitory synaptic efficacy at two major classes of cerebellar neurons. These tandem findings suggest that nAChRs may present a potential drug target for disorders involving the cerebellum.
机译：尽管最近的研究描述了哺乳动物小脑中存在的特定烟碱亚型，但对其在小脑中的位置或功能了解甚少。由于近来小脑中的烟碱样受体（nAChRs）与自闭症谱系障碍的病理学有关，因此这引起了越来越多的关注。为了更好地了解这些异聚nAChR在小脑回路中的作用及其作为药物开发靶标的治疗潜力，我们使用了各种化学和立体定位的病变模型，结合切片电生理学来研究特定的异聚nAChR亚型如何影响周围的小脑电路。使用N-（2-氯乙基）-N-乙基-2-溴苄胺盐酸盐，对氯苯丙胺和Pendunculototomy病变后小脑中放射性标记nAChRs的亚基特异性免疫沉淀，我们发现大多数（如果不是全部）小脑烟碱样受体是存在于小脑本身内的细胞中，而不存在于小脑外传入细胞中。此外，我们证明小脑固有的含β4而不是含β2的nAChRs可以在小脑神经元的两大类中调节抑制性突触功效。这些串联的发现表明，nAChRs可能为涉及小脑的疾病提供潜在的药物靶标。

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