Histamine H 1 receptor on astrocytes and neurons controls distinct aspects of mouse behaviour

Histamine is an important neurotransmitter that contributes to various processes, including the sleep-wake cycle, learning, memory, and stress responses. Its actions are mediated through histamine H -H receptors. Gene knockout and pharmacological studies have revealed the importance of H receptors in learning and memory, regulation of aggression, and wakefulness. H receptors are abundantly expressed on neurons and astrocytes. However, to date, studies selectively investigating the roles of neuronal and astrocytic H receptors in behaviour are lacking. We generated novel astrocyte- and neuron-specific conditional knockout (cKO) mice to address this gap in knowledge. cKO mice showed cell-specific reduction of H receptor gene expression. Behavioural assessment revealed significant changes and highlighted the importance of H receptors on both astrocytes and neurons. H receptors on both cell types played a significant role in anxiety. Astrocytic H receptors were involved in regulating aggressive behaviour, circadian rhythms, and quality of wakefulness, but not sleep behaviour. Our results emphasise the roles of neuronal H receptors in recognition memory. In conclusion, this study highlights the novel roles of H receptors on astrocytes and neurons in various brain functions.