CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; FMUC-Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; FMUC-Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Neurosci Lett. 2014 Apr 30;566:106-10. doi: 10.1016/j.neulet.2014.02.018. Epub 2014 Mar 4.
The striatum is the primary input station of the basal ganglia network, playing an essential role in sensorimotor, cognitive and motivational functions. Nicotinic acetylcholine receptors (nAChRs) were identified in nerve terminals of the striatum, where they are known to modulate neurotransmitter release, therefore critically regulating striatal functions. However, the subsynaptic (i.e. pre-, post- and extra-synaptic) localization of the different nAChRs subtypes present in the striatal synapses is still unclear, which might be associated with different roles in the control of synaptic transmission. In the present study we analyzed the subsynaptic distribution of particularly relevant nAChRs subunits, namely α7, α6, α4 and β2, in rat and mice striatal synapses (synaptosomes). In the rodent striatum we found that the α7 subunit, which predominantly forms homomeric nAChRs, was mainly present at the presynaptic active zone. The α4 and β2 subunits displayed a similar distribution, being primarily present at the presynaptic and/or extrasynaptic zones (mice and rats, respectively), which was expected since these two subunits together form heteropentameric nAChRs. In contrast, the α6 subunit was mainly present in the postsynaptic fraction, albeit being also present in pre- and extra-synaptic fractions. Altogether, this work details the striatal subsynaptic distribution of some of the main nAChRs subunits, underlining the possible relevance of striatal nAChRs in controlling neurotransmission, with potential relevance for Parkinson's disease, nicotine addiction and other dopaminergic disorders.
纹状体是基底神经节网络的主要输入站，在感觉运动、认知和动机功能中发挥着重要作用。烟碱型乙酰胆碱受体 (nAChRs) 在纹状体的神经末梢被鉴定出来，已知它们可以调节神经递质的释放，因此对纹状体的功能起着至关重要的调节作用。然而，纹状体突触中存在的不同 nAChRs 亚基的亚突触（即前突触、后突触和突触外）定位仍不清楚，这可能与它们在调节突触传递中的不同作用有关。在本研究中，我们分析了在大鼠和小鼠纹状体突触（突触体）中特别相关的 nAChRs 亚基，即 α7、α6、α4 和 β2 的亚突触分布。在啮齿动物纹状体中，我们发现主要形成同源 nAChRs 的 α7 亚基主要存在于突触前活性区。α4 和 β2 亚基的分布相似，主要存在于突触前和/或突触外区（分别在小鼠和大鼠中），这是预期的，因为这两个亚基共同形成异五聚体 nAChRs。相比之下，α6 亚基主要存在于突触后部分，尽管也存在于前突触和突触外部分。总的来说，这项工作详细描述了一些主要的 nAChRs 亚基在纹状体中的亚突触分布，强调了纹状体 nAChRs 在控制神经传递中的可能重要性，这与帕金森病、尼古丁成瘾和其他多巴胺能障碍等疾病有潜在的关联。
