Heterogeneous Distribution of the Serotonin 5-HT1A Receptor mRNA in Chemically Identified Neurons of the Mouse Rostral Brainstem: Implications for the Role of Serotonin in the Regulation of Wakefulness and REM Sleep
Heterogeneous Distribution of the Serotonin 5-HT1A Receptor mRNA in Chemically Identified Neurons of the Mouse Rostral Brainstem: Implications for the Role of Serotonin in the Regulation of Wakefulness and REM Sleep
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DOI：
10.1002/cne.22331
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发表时间：
2010-07-15
影响因子：
2.5
通讯作者：
Fabre, Veronique
中科院分区：
文献类型：
--
作者：
Bonnavion, Patricia;Bernard, Jean-Francois;Fabre, Veronique
5-HT 1A受体（5-HT 1AR）在5-HT抑制啮齿动物快速眼动（REM）睡眠中起关键作用。然而，介导这种影响的神经元网络大多是未知的，特别是在小鼠中。这使我们映射5-HT1AR mRNA，通过原位杂交组织化学（ISHH），并通过双重ISHH和ISHH结合免疫组织化学来表征5-HT1AR mRNA阳性神经元的神经元表型，在整个小鼠喙部脑干中，快速眼动睡眠和皮质激活的产生的关键区域。在中缝背核（DR）、中缝正中核（MnR）、B9核和脚间核（IP）的多数5-HT神经元中发现了5-HT 1AR mRNA。5-HT1AR mRNA阳性神经元也被确定在个别集群的γ-氨基丁酸（GABA）能神经元的DR和神经元的一个未定表型的MnR。此外，Gudden背侧被盖核腹侧部（DTg）、IP和中脑深核尾侧部（DpMe）的GABA能神经元，以及散在分布于脑桥尾侧网状核（PnC）和密集分布于臂旁内侧亚核（PBil）的GABA能神经元也表达5-HT 1AR mRNA。相反，在脑干胆碱能神经元和儿茶酚胺能神经元中通常没有检测到特异性5-HT1AR相关的ISHH信号。这些结果强调了5-HT1AR作为自身受体的作用和小鼠脑中DR和MnR内5-HT1AR表达神经元的表型异质性。它们还为理解5-HT1AR对REM睡眠和觉醒的影响提供了神经解剖学基础。神经学比较杂志518：2744 - 2770，2010. (C)2010 Wiley-Liss，Inc.
The 5-HT1A receptor (5-HT1AR) plays a key role in the inhibitory influence of serotonin (5-HT) on rapid eye movement (REM) sleep in rodents. However, the neuronal networks mediating such influence are mostly unknown, notably in the mouse. This led us to map 5-HT1AR mRNA, by in situ hybridization histochemistry (ISHH), and to characterize the neuronal phenotype of 5-HT1AR mRNA-positive neurons by dual ISHH and ISHH combined with immunohistochemistry, throughout the mouse rostral brainstem, a pivotal region for the generation of REM sleep and cortical activation. 5-HT1AR mRNA was found in most 5-HT neurons in the dorsal raphe (DR), the median raphe (MnR), the B9, and the interpeduncular (IP) nuclei. 5-HT1AR mRNA-positive neurons were also identified in individualized clusters of gamma-aminobutyric acid (GABA)ergic neurons in the DR and in neurons of an undetermined phenotype in the MnR. In addition, 1) GABAergic neurons of the ventral portion of Gudden's dorsal tegmental nucleus (DTg), the IP, and the caudal portion of the deep mesencephalic nucleus (DpMe), and 2) glutamatergic neurons scattered in the caudal pontine reticular nucleus (PnC) and densely packed in the internal lateral parabrachial subnucleus (PBil) also expressed 5-HT1AR mRNA. In contrast, no specific 5-HT1AR-related ISHH signal was generally detected in brainstem cholinergic and catecholaminergic neurons. These results emphasize the role of 5-HT1AR as an autoreceptor and the phenotypical heterogeneity of 5-HT1AR-expressing neurons within the DR and the MnR in the mouse brain. They also provide a neuroanatomical basis for understanding the influence of 5-HT1AR on REM sleep and wakefulness. J. Comp. Neurol. 518:2744-2770, 2010. (C) 2010 Wiley-Liss, Inc.