Histamine-immunoreactive neurons and their innervation of visual regions in the cortex, tectum, and thalamus in the primate Macaca mulatta.

The histaminergic system is involved in the control of arousal in the brain and may impact significantly on visual processing. However, little is known about the histaminergic innervation of visual areas, or the histamine system in the primate brain, in general. We examined in Macaca mulatta the location of histamine-immunoreactive neurons and the innervation of important cortical and subcortical visual areas by histamine-immunoreactive axons. Brain sections were treated with an antibody to histamine and processed with standard immunohistological procedures. Histamine-immunoreactive neurons (20-45 microns in diameter) were localized bilaterally in the hypothalamus, particularly in ventral, lateral, posterior, and perimammillary hypothalamic areas. These hypothalamic cells appear to provide the sole neural source of histamine in the macaque brain. A plexus of varicose histamine-immunoreactive axons was present throughout the superior colliculus, the dorsal and ventral lateral geniculate nuclei of the thalamus, the reticular nucleus of the thalamus, the lateral posterior/pulvinar complex, and the visual cortex, including areas 17, 18, and the nearby extrastriate cortex. The axons nearly homogeneously innervated every region and layer in these structures, except for an increase in density in layer 1 of the visual cortex and in the superficial-most layers of the superior colliculus. Histaminergic axons broadly innervated every visual region examined. In comparison with the other aminergic and the cholinergic projection systems, which show considerable projection specificity, the histaminergic projection exhibited great homogeneity. The breadth of the distribution of histaminergic axons ensures that virtually all levels of visual processing in the primate can be influenced, either directly or indirectly, by the neuromodulatory effects of histamine.