Developmental roles of brain histamine

Histamine appears early during brain development, has been shown to regulate fetal and adult brain-derived stem cells in a receptor type-dependent manner, and has widespread actions on systems involved in arousal and movement. Developmental studies in both rodents and zebrafish have elucidated the spatiotemporal patterning of the histaminergic system and, in zebrafish, have revealed the mechanisms whereby histamine regulates the number of hypocretin/orexin (hcrt) neurons, which in turn may regulate the number of histaminergic cells. Recent demonstrations of increased numbers of histaminergic neurons in patients with narcolepsy highlight the importance, for our understanding of both normal and pathological brain function, of understanding these interactions. Here, we review recent research into the developmental roles of histamine and suggest key areas for future research.