Brainstem innervation of prefrontal and anterior cingulate cortex in the rhesus monkey revealed by retrograde transport of HRP.

The cells of origin of projections from the brainstem to the dorsolateral and orbital prefrontal granular cortex and to the anterior cingulate cortex of the rhesus monkey were analyzed by means of retrograde axonal transport of the enzyme horseradish peroxidase (HRP). Following injections in various portions of the dorsolateral prefrontal and in the cingulate cortex, HRP-positive neurons were found in three main locations: (1) the ventral midbrain including the anterior ventral tegmental area, the medial one-third of the substantia nigra pars compacta, and the retrorubral nucleus; (2) the central superior nucleus and the dorsal raphe nucleus, primarily in its caudal subdivision; and (3) the locus coeruleus and adjacent medial parabrachial nucleus. Labeled neurons in the raphe nuclei and locus coeruleus were distributed bilaterally. A basically similar pattern of labeled somata was found in the brainstem with HRP injections in the orbital prefrontal cortex. Scattered HRP-positive cells were found throughout the ipsilateral ventral tegmental area and in ventromedial portions of the retrorubral nucleus, and a large number of HRP-positive cells were distributed bilaterally in the dorsal raphe and central superior nuclei as well as the dorsolateral pontine tegmentum. However, in contrast to the results obtained with injections on the dorsolateral and medial aspects of the hemisphere, labeled neurons were not found in any portion of the substantia nigra. The neurons labeled retrogradely after injection of HRP in these various regions of the frontal lobe in rhesus monkey correspond both in location and morphology to the monoamine-containing neurons of the brainstem and are thus very likely the source of dopamine, norepinephrine, and serotonin found in the frontal cortex of the same species.