Amygdala intercalated cells form an evolutionarily conserved system orchestrating brain networks

The amygdala attributes valence and emotional salience to environmental stimuli and regulates how these stimuli affect behavior. Within the amygdala, a distinct class of evolutionarily conserved neurons form the intercalated cell (ITC) clusters, mainly located around the boundaries of the lateral and basal nuclei. Here, we review the anatomical, physiological and molecular characteristics of ITCs, and detail the organization of ITC clusters and their connectivity with one another and other brain regions. We describe how ITCs undergo experience-dependent plasticity and discuss emerging evidence demonstrating how ITCs are innervated and functionally regulated by neuromodulatory systems. We summarize recent findings showing that experience alters the balance of activity between different ITC clusters, thereby determining prevailing behavioral output. Finally, we propose a model in which ITCs form a key system for integrating divergent inputs and orchestrating brain-wide circuits to generate behavioral states attuned to current environmental circumstances and internal needs.