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

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.