Forebrain projections to the periaqueductral gray in the monkey, with observations in the cat and rat

There is considerable evidence that the midbrain periaqueductal gray (PAG) is involved in visceral, emotive, and sexual responses and in endogenous analgesic effects. To see which of the forebrain areas directly influence the PAG, small injections of horseradish peroxidase were made into the various regions of monkey, cat, and rat PAG. Despite the fact that different regions of the PAG were injected in separate animals the majority of the forebrain areas labeled remained constant. Retrogradely filled pyramidal neurons in layer V were found in the frontal lobe in areas 6, 8, 9, 10, 13, and 24. Labeled neurons also appeared in the amygdala, preoptic area, and the anterior, dorsal, periventricular, ventromedial, periarcuate, lateral, and posterior hypothalamic nuclei. The main route for the hypothalamic → PAG projection appeared to be via the periaqueductal bundle which immediately borders on the cerebral aqueduct. Labeled neurons were also observed in the zona incerta, mesencephalic reticular formation, deep layers of the superior colliculus, and the nucleus cuneiformis. Most labeling was ipsilateral to the injection site although a small but consistent contralateral labeling was present. Therefore a strict subdivision of the PAG based on each subnucleus having its own unique set of connections seems inappropriate. There were few striking differences found in the forebrain areas that project to the PAG in the three species examined. These results are discussed in terms of the possible contribution these forebrain areas have in regulating the PAG with regard to its functions as a visceral, nociceptive, and cognitive integrator.