Resolving amygdala microcircuits: implications for function

Resolving amygdala microcircuits: implications for function Years of neuroimaging research in human psychiatric disorders, including at-risk populations, highlights alterations in circuits involving the amygdala. 'Fingerprints' of specific cortical and amygdala correlated activity promise to help identify specific circuits involved in particular diseases. Despite this, the structural or 'wiring' details of cortical-amygdala circuits remain obscure. Here we examine the idea that the unique symptom profiles across heterogeneous disorders are best explained by how different combinations of cortical inputs form 'microcircuits' in the amygdala, each associated with unique output paths. This proposal focuses on cortical nodes that project to the amygdala, and are frequently involved in psychiatric conditions. The subgenual anterior cingulate (sgACC) and rostral agranular insula (Ia) mediate internal body sensations, or 'interoceptive states'; the perigenual ACC (pgACC) and the middle, dysgranular insula (Id) are regions involved in 'social monitoring' and affiliative responses. Using dual anterograde tract tracing approaches in the same animal, our preliminary data show that afferent terminals from pgACC 'social monitoring' nodes are always 'nested' in terminals arriving from the sgACC ('interoceptive) in the amygdala. sgACC terminals cover a broader territory. This overlap creates terminal 'hotspots' of sgACC and pgACC afferent integration. At the cellular level, sgACC and pgACC associated terminals almost always co-contacted pyramidal cells (rather than segregating to different populations), and did so in a very stable ratio. These data indicate normal, tight afferent control, and integration of incoming information, onto amygdala neurons in these 'hotspots'. This terminal balance suggests an anatomic substrate that may be altered in various disease states. We also found that amygdala neurons in converging sgACC/pgACC hotspots had distinct projections back to the cortex, which were different than from non-hotspots regions. In this proposal, we dissect microcircuits involving sgACC, Ia, pgACC, and Id. We begin with determining specific cortical networks involving these nodes (Aim 1), then examine how afferent terminals from different two-node systems overlap or segregate in the amygdala, including at the cellular level (Aim 2A, B). We then examine whether amygdala neurons in converging afferent 'hotspots' have unique outputs to the cortex (Aim 3).