The goal of this project is to determine the organization of a neural circuit involved in integrating emotional information with information from the external environment. The brain regions involved in this circuit include the amygdala, the mediodorsal thalamic nucleus, and posterior orbitofrontal cortex (pOFC), but their synergistic projections and synaptic interactions are unknown. This circuit is thought to be activated in associating stimuli with emotional value in order to flexibly change behavior when circumstances change. By studying these circuits at the systems and synaptic level, it will be possible to develop a more sophisticated and complete model of their interactions. The working hypothesis is that there are two key paths to pOFC: one sends emotional information, and another serves to drown out distracters. In this model, emotional information is sent from the amygdala through the thalamic mediodorsal nucleus (MD) to pOFC, while a separate pathway from the amygdala directly to pOFC acts to suppress distracting stimuli. This model would allow flexible, selective representation of emotional information within pOFC for use in decision-making and attentional processes in other prefrontal regions. This model will be tested by studying thalamic and amygdalar projections to pOFC. This will be accomplished by injection of distinct neural tracers into the amygdala and the thalamic MD nucleus in rhesus monkeys to map their projections to pOFC. Using light, fluorescence and electron microscopy, the distribution and size of projection terminals from the amygdala and MD, and their inhibitory or excitatory targets in different layers of pOFC will be compared to determine their relative contributions. Another study will focus on the question of whether neurons in the thalamic MD nucleus that project to pOFC are innervated directly by the amygdala, with a goal to investigate the sequential flow of signals for emotions. These analyses will provide critical information that is prerequisite to understanding the functional significance of the amygdala and thalamic inputs to pOFC. Together these experiments will provide a detailed and cohesive picture of the organization of the circuit connecting the pOFC, thalamic MD, and amygdala. This circuit has a critical role in normal behavior, and its dysfunction has been linked to phobias, obsessive-compulsive disorder, and autism. Information about the connections and synapses in this circuit will make it possible to develop a circuit model to investigate how abnormalities at different nodes lead to psychiatric disorders and to develop therapies. PUBLIC HEALTH RELEVANCE: The goal of this project is to determine the organization of a circuit in the primate brain related to emotion, dysfunction of which has been linked to several psychiatric disorders. Information on the connections within this pathway will provide insight as to how abnormalities in this pathway could lead to psychiatric disorders. Greater understanding of the pathway mechanisms underlying psychiatric disorders is critical to developing effective treatments.