Anatomical characterization of the neuropeptide S system in the mouse brain by in situ hybridization and immunohistochemistry

Neuropeptide S (NPS) is the endogenous ligand for GPR154, now referred to as neuropeptide S receptor (NPSR). Physiologically, NPS has been characterized as a modulator of arousal and has been shown to produce anxiolytic-like effects in rodents. Neuroanatomical analysis in the rat revealed that the NPS precursor mRNA is strongly expressed in the brainstem in only three distinct regions: the locus coeruleus area, the principal sensory trigeminal nucleus, and the lateral parabrachial nucleus. NPSR mRNA expression in the rat is widely distributed, with the strongest expression in the olfactory nuclei, amygdala, subiculum, and some cortical structures, as well as various thalamic and hypothalamic regions. Here we report a comprehensive map of NPS precursor and receptor mRNA expression in the mouse brain. NPS precursor mRNA is only expressed in two regions in the mouse brainstem: the Kolliker-Fuse nucleus and the pericoerulear area. Strong NPSR mRNA expression was found in the dorsal endopiriform nucleus, the intra-midline thalamic and hypothalamic regions, the basolateral amgydala, the subiculum, and various cortical regions. In order to elucidate projections from NPS-producing nuclei in the brainstem to NPSR-expressing structures throughout the brain, we performed immunohistochemical analysis in the mouse brain by using two polyclonal anti-NPS antisera. The distribution of NPS-immunopositive fibers overlaps well with NPSR mRNA expression in thalamic and hypothalamic regions. Mismatches between NPSR expression and NPS-immunoreactive fiber staining were observed in hippocampal, olfactory, and cortical regions. These data demonstrate that the distribution pattern of the central NPS system is only partially conserved between mice and rats. J. Comp. Neurol. 519:1867–1893, 2011. © 2011 Wiley-Liss, Inc.