The goal of the proposed studies is to investigate the contribution of prefrontal and amygdalar pathways to memory-related cortices in the medial temporal lobe (MTL). The overarching hypothesis is that the interaction of these pathways with MTL rhinal cortices constitutes a circuit that integrates attentional context with emotional and mnemonic information. The caudal portion of the medial prefrontal cortex in the anterior cingulate (ACC) is thought to be involved in monitoring on-going behavior pertaining to memory of previously learned outcomes, but how pathways from this cortex impinge on the MTL is not well understood. Recent evidence has shown that the medial prefrontal cortex facilitates communication between the rhinal cortices of the MTL. These findings suggest that ACC plays an important role in corticohippocampal processing, an issue compounded by the fact that information transfer, both to, and from the hippocampus is gated via local inhibition within the rhinal cortices. The proposed studies will address the largely unexplored synaptic interactions of the ACC and amygdala with excitatory and inhibitory systems within the rhesus monkey MTL to investigate: 1) projections from the medial prefrontal cortex to rhinal cortices;2) whether ACC axons synapse with distinct classes of inhibitory and excitatory circuits in rhinal cortices;3) whether projections from the ACC and amygdala are positioned to act synergistically in rhinal cortices. Prefrontal pathways will be labeled with multiple distinct neural tracers combined with double or triple labeling immunohistochemistry to map axonal terminations as well as excitatory and inhibitory neurons within MTL. Data will be collected at the light, confocal and electron microscope level for quantitative analyses. Understanding how the ACC and the amygdala impinge upon the rhinal cortical mnemonic circuit, and by extension how attentional context is integrated with mnemonic and emotional information, is critical for understanding nominal memory function and for gaining insight into the pathologies observed in anxiety disorders. PUBLIC HEALTH RELEVANCE: Clinical findings and imaging studies in patients suffering from anxiety disorders, including post traumatic stress disorder, indicate that symptoms may manifest due to disruptions in the ACC- amygdala-rhinal cortical circuit affecting the integration of context with emotionally salient memories. The proposed studies address the synaptic interactions underlying the synthesis of contextual (ACC) and emotional (amygdala) information with memory related circuits (rhinal cortices), which is prerequisite to the development of therapies for these psychiatric disorders.