DESCRIPTION (provided by applicant): Integrating social networks through amygdalostriatal paths A longstanding focus of our laboratory is the identification of pathways through the primate amygdala that are positioned to mediate symptomatology of severe mental illnesses. Because emotional dysregulation in psychiatric syndromes is often expressed as maladaptive social function, the proposed studies examine how networks involved in social function interact with 'salience detection' pathways in the amygdala and striatum of the nonhuman primate. Tract tracing studies in nonhuman primate enable more accurate interpretation of neuroimaging results in humans, and are a critical bridge for understanding details of primate brain structure on a cellular level. In this set of studies, we examine two cortical networks that are frequently dysregulated in psychiatric illnesses: the 'salience detection' network (areas 25/32, agranular insula) which monitors internal physiologic states to 'mark' salient cues, and the 'social monitoring' network (areas 24/14/dysgranular cortex), which detects and interprets the meaning and value of others' actions. These networks are often considered physiologically distinct. However, since emotional dysregulation in human illness is frequently expressed in misinterpretation of social cues, integration of 'salience' and 'social monitoring' networks must exist. We propose that specific circuits through the amygdala and striatum are substrates for this integration. Aim 1 will map the boundaries of inputs from 'social-monitoring-associated' cortex in the amygdala, and the resulting organization of outputs to the striatum. In Aim 2, we will place retrograde tracers into novel striatal sectors targeted by 'social' corticoamygdala-striatal path in Aim 1 to determine whether they are defined by direct cortical projections from the social monitoring network. In Aim 3 we will examine the amygdala under higher power, to determine whether converging inputs terminals from nodes of the 'salience' and 'social monitoring' networks predominantly synapse on the same neural population, or on separate subpopulations.

PUBLIC HEALTH RELEVANCE: Misinterpretation of social cues is an important problem for patients with illnesses ranging from psychotic disorders, to anxiety, to autism. These studies in normal animals will examine at the microscopic level how circuits carrying information about social cues are modulated by circuits that tag information with emotional importance.