Previous research on the role of HDC within the central nervous system lends additional support to our genetic data. Although HDC expression is highly constrained within the posterior hypothalamus, axons from histamine-containing neurons project throughout the brain. Histaminergic signaling is mediated by four known G protein–coupled receptors — H1 through H4 — that are located both presynaptically (H3 and H4) and postsynaptically (H1, H2, and H3) and are known to modulate circadian rhythms, appetite, memory, and behavior.12 Moreover, H2 and H3 receptors are highly enriched in the striatum and cortex, regions widely implicated in the pathophysiology of Tourette's syndrome.12
