Comprehensive mapping of histamine H₁ receptor mRNA in the mouse brain

Histamine H₁ receptor (H₁R) in the central nervous system plays an important role in various functions, including learning and memory, aggression, feeding behaviors, and wakefulness, as evidenced by studies utilizing H₁R knockout mice and pharmacological interventions. Although previous studies have reported the widespread distribution of H₁R in the brains of rats, guinea pigs, monkeys, and humans, the detailed distribution in the mouse brain remains unclear. This study provides a comprehensive description of the distribution of H₁R mRNA in the mouse brain using two recently developed techniques: RNAscope and in situ hybridization chain reaction, both of which offer enhanced sensitivity and resolution compared to traditional methodologies such as radioisotope labeling, which were used in previous studies. The H₁R mRNA expression was observed throughout the entire brain, including key regions implicated in sleep-wake regulatory functions, such as the pedunculopontine tegmental nucleus and dorsal raphe. Additionally, strong H₁R mRNA signals were identified in the paraventricular hypothalamus and ventromedial hypothalamus, which may explain the potential mechanisms underlying histamine-mediated feeding regulation. Notably, we identified strong H₁R mRNA expression in previously unreported cerebral regions, such as the dorsal endopiriform nucleus, bed nucleus of the accessory olfactory tract, and postsubiculum. These findings significantly contribute to our understanding of the multifaceted roles of H₁R in diverse brain functions.