Connections of midbrain periaqueductal gray in the monkey. I. Ascending efferent projections

To obtain a comprehensive map of the ascending projection of the midbrain periaqueductal gray, small amounts of [³H]leucine were injected into discrete regions of the periaqueductal gray (PAG) of the monkey. Despite the fact that different regions of the PAG were injected in separate animals, the majority of the PAG's efferent projections to the forebrain remained constant. The diencephalic projection areas include the nucleus reticularis thalami, the nucleus medialis dorsalis, the midline thalamic nuclei, the intralaminar thalamic nuclei, the preoptic area, and the anterior, dorsal, periventricular, ventromedial, periarcuate, lateral, and posterior hypothalamic nuclei. More caudal areas receiving a projection from the PAG include the zona incerta and the mesencephalic reticular formation. The main route for PAG-diencephalic projections is through the periventricular bundle. This implies that if a stimulating electrode was placed in this region, both the diencephalic → PAG and PAG → diencephalic pathways would be stimulated. This observation may explain the wide variety of side effects often encountered in stimulation-produced analgesia in humans. These results support our hypothesis that the PAG functions as a visceral, nociceptive, and cognitive integrator.