The long-term goal of the proposed research program is to understand the influence of pathways underlying emotional and cognitive processes on the central executive functions of the prefrontal cortex. Functional studies in humans indicate that the executive functions of the prefrontal cortex are guided by input from structures associated with cognitive and emotional processes. The goal of the proposed studies is to investigate the pattern and synaptology of pathways linking the orbitotofrontal cortex with the amygdala, in common pathways with sensory association, polymodal and thalamic structures that have key roles in emotion and cognition. The working hypothesis is that the orbitofrontal cortex has dual effects on the amygdala by targeting two distinct systems with opposite effects on autonomic control. Moreover, the selection of each pathway is contingent on emotional context, derived through pathways linking sensory association areas, orbitofrontal areas, and thalamic structures with the amygdala. This hypothesis will be tested by: (1) Determining the density and synaptic interactions of axons from orbitofrontal areas onto specialized inhibitory and excitatory systems in the amygdala; (2) Comparing the laminar origin of projections from sensory association and orbitofrontal areas to the amygdala, that may underlie the flow of information processing for emotions; (3) Investigating the linkage of the thalamic motor-related ventral anterior nucleus with the amygdala, and its synaptic interactions with prefrontal areas, in pathways associated with emotions and executive control. Neural pathways will be labeled with bi-directional tracers, combined with double-labeling for inhibitory neurons and projection neurons, and processed for correlated light and electron microscopic analysis. The proposed studies will establish the foundation to understand the unique contribution of orbitofrontal, sensory association, and thalamic structures in emotions, and the disconnection of cognitive from emotional processes in psychiatric and neurologic diseases.