ABSTRACT
Histamine in histaminergic neurons is synthesized from histidine through decarboxylation by histidine-decarboxylase (HDC), a pyridoxal 5'-phosphate-dependent enzyme highly conserved throughout the animal kingdom. Histamine in the brain is inactivated in the extracellular space by methylation through neuronal histamine N-methyltransferase. A histaminergic system in rat brain arises transiently, ~2 weeks after gestation, in the midbrain at the location of adult serotonergic neurons. Histamine levels and turnover are elevated in hibernating ground squirrels in contrast to other transmitter systems. The histaminergic neurons receive innervation from the preoptic area of the hypothlamus, the septum, the prefrontal cortex, the subiculum, and the dorsal tegmentum —regions that are targets of tuberomammillary nucleus (TMN) projections. Antibodies against histamine stain the histaminergic fibers better than antibodies against HDC, although both HDC and histamine are present in TMN somata and axon varicosities. Histamine directly facilitates N-methyl-D-aspartate receptors and enhances excitatory transmission. Histaminergic fibers in the spinal cord coming from the TMN are extensive in higher mammalian species.
