Using the retrograde transport of horseradish peroxidase (HRP), a study has been made of projections to the ventral tegmental area of Tsai (VTA) and related dopaminergic cell groups (A 10). In order to minimise the possibility of damage to fibres of passage, a technique was evolved for the microiontophoresis of HRP such that minimal current strengths and durations were applied. In addition to a sham injection, control injections were also made to the medial leminiscus, red nucleus, deep tegmental decussations, mesencephalic reticular formation and brachium conjunctivum. Following HRP injections confined to the areas of the VTA containing the dopamine cell groups, labelled neurons appeared in prefrontal cortex, dorsal bank of rhinal sulcus, nucleus accumbens, bed nucleus of stria terminalis, amygdala, diagonal band of Broca, substantia innominata, magnocellular preoptic area, medial and lateral preoptic areas, anterior, lateral and postero-dorsal hypothalamus, lateral habenular, nucleus parafascicular nucleus of thalamus, superior colliculus, nucleus raphe dorsalis, nucleus raphe magnus and pontis, dorsal and ventral parabrachial nuclei, locus coeruleus and deep cerebellar nuclei. Regions containing catecholamine goups A 1, A 5, A 6, A 7, A 9, A 13 and the serotonin group B 7 corresponded to the topography of labeled cell groups. Injections of HRP to the interfascicular nucleus resulted in labeling predominantly confined to the medial habenular and median raphe nuclei. The results are discussed in relation to the known connections of these regions. Other regions of the brain labelled by VTA injections are assessed in relation to control injections and the limitations of the HRP technique.
A review of the organisation of some of these afferents in relation to the known cortical-subcortical-mesencephalic projection systems, suggests that the VTA is in a position to receive information from a massively convergent system derived ultimately from the entire archi-, paleo-, and neo-cerebral cortices. In addition A 10 dopaminergic neurons are known to project to restricted regions of both pre-frontal and entorhinal cortices, which themselves also receive massively convergent association cortico-cortical connections. It would appear reasonable to propose that these neurons perform a correspondingly important integrative function.