Pii: S0306-4522(00)00585-6

ÐThe prefrontal cortex in rhesus monkeys is a heterogeneous region by structure, connections and function. Caudal medial and orbitofrontal cortices receive input from cortical and subcortical structures associated with emotions, autonomic function and long-term memory, while lateral prefrontal cortices are linked with structures associated with working memory. With the aid of neural tracers we investigated whether functionally distinct orbitofrontal, medial and lateral prefrontal cortices have speci®c or common connections with an ascending modulatory system, the basal forebrain. Ascending projections originated in the diagonal band and the basalis nuclei of the basal forebrain in regions demarcated by choline acetyltransferase. Although the origin of projections from the basal forebrain to lateral, medial and orbitofrontal cortices partially overlapped, projections showed a general topography. The posterior part of the nucleus basalis projected preferentially to lateral prefrontal areas while its rostrally adjacent sectors projected to medial and orbitofrontal cortices. The diagonal band nuclei projected to orbitofrontal and medial prefrontal areas. Cortical and subcortical structures that are interconnected appear to have a similar pattern of connections with the basal forebrain. In comparison to the ascending projections, the descending projections were speci®c, originating mostly in the posterior (limbic) component of medial and orbitofrontal cortices and terminating in the diagonal band nuclei and in the anterior part of the nucleus basalis. In addition, prefrontal limbic areas projected to two other systems of the basal forebrain, the ventral pallidum and the extended amygdala, delineated with the striatal-related markers dopamine, adenosine 3 0:5 0-monophosphate regulated phosphoprotein of Mr 32 kDa, and the related phosphoprotein Inhibitor-1. These basal forebrain systems project to autonomic nuclei in the hypothalamus and brainstem. We interpret these results to indicate that lateral prefrontal areas, which have a role in working memory, receive input from, but do not issue feedback projections to the basal forebrain. In contrast, orbitofrontal and medial prefrontal areas, which have a role in emotions and long-term memory, have robust bidirectional connections with the basal forebrain. Moreover, orbitofrontal and medial prefrontal cortices target the ventral pallidum and the extended amygdala, through which high-order association areas may activate motor autonomic structures for the expression of emotions. q 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.