Le Novère N, Zoli M, Changeux J P
CNRS URA 1284, Pasteur Institute, Paris, France.
Eur J Neurosci. 1996 Nov;8(11):2428-39. doi: 10.1111/j.1460-9568.1996.tb01206.x.
Although the neuronal nicotinic receptor alpha 6 subunit was cloned several years ago, its functional significance remains to be investigated. Here we describe an in situ hybridization study of the mRNA for this subunit in the adult rat central nervous system using oligonucleotide probes. Specific alpha 6 mRNA labelling was restricted to a few nuclei throughout the brain; it was particularly high in several catecholaminergic nuclei [the locus coeruleus (A6), the ventral tegmental area (A10) and the substantia nigra (A9)] at levels significantly higher than those found for any other known nicotinic receptor subunit mRNA. Labelling for alpha 6 mRNA was also detected at lower levels in the reticular thalamic nucleus, the supramammillary nucleus and the mesencephalic V nucleus. Some cells of the medial habenula (medioventral part) and of the interpeduncular nucleus (central and lateral parts) were also labelled. The distribution of alpha 6 mRNA was compared with the distribution of the other known nicotinic acetylcholine receptor subunit mRNAs. In several nuclei, the expression of alpha 6 was complementary to those of other alpha subunits. Moreover, some of the cell groups (such as the substantia nigra, the ventral tegmental area and the locus coeruleus) previously thought to contain mainly alpha 3 mRNA in fact were found to contain high levels of alpha 6 mRNA. Finally, we found extensive colocalization of alpha 6 and beta 3, indicating the possible existence of nicotinic receptor hetero-oligomers containing both subunits. The present results show that alpha 6 is the major nicotinic acetylcholine receptor alpha subunit expressed in dopaminergic cell groups of the mesencephalon and noradrenergic cells of the locus coeruleus. This suggests the involvement of the alpha 6 subunit in some of the major functions of central nicotinic circuits, including the modulation of locomotor behaviour and reward.
尽管神经元烟碱型受体α6亚基在数年前就已被克隆，但其功能意义仍有待研究。在此，我们使用寡核苷酸探针描述了成年大鼠中枢神经系统中该亚基mRNA的原位杂交研究。特异性α6 mRNA标记局限于整个大脑的少数核团；在几个儿茶酚胺能核团[蓝斑（A6）、腹侧被盖区（A10）和黑质（A9）]中特别高，其水平显著高于任何其他已知烟碱型受体亚基mRNA的水平。在丘脑网状核、乳头体上核和中脑V核中也检测到较低水平的α6 mRNA标记。内侧缰核（中间腹侧部分）和脚间核（中央和外侧部分）的一些细胞也有标记。将α6 mRNA的分布与其他已知烟碱型乙酰胆碱受体亚基mRNA的分布进行了比较。在几个核团中，α6的表达与其他α亚基的表达互补。此外，一些先前认为主要含有α3 mRNA的细胞群（如黑质、腹侧被盖区和蓝斑）实际上被发现含有高水平的α6 mRNA。最后，我们发现α6和β3广泛共定位，表明可能存在同时包含这两个亚基的烟碱型受体异源寡聚体。目前的结果表明，α6是中脑多巴胺能细胞群和蓝斑去甲肾上腺素能细胞中表达的主要烟碱型乙酰胆碱受体α亚基。这表明α6亚基参与了中枢烟碱回路的一些主要功能，包括对运动行为和奖赏的调节。
