An amygdala circuit that supresses social engagement

Innate social behaviors, such as mating and fighting, are fundamental to animal reproduction and survival. However, social engagements are associated with risks for the individual, such as pathogenic infection and physical injury. Little is known about the neural mechanism that allows for appropriate risk assessment and the suppression of hazardous social interactions. We have identified the posteromedial nucleus of the cortical amygdala (COApm) as a locus required for the suppression of mating with an unhealthy female and aggressive behaviors towards a dominant male intruder. Using anatomical tracing, functional imaging, and circuit-level epistatic analyses, we show that suppression of social engagements is mediated by the COApm projections onto the glutamatergic population of the medial amygdalar nucleus (MEA). We further show that this projection that governs social engagements is demarcated by expression of both the neuromodulator thyrotropin-releasing hormone (TRH) in the COApm and the TRH-receptor (TRHR) in the postsynaptic MEA glutamatergic neurons. Modulating TRH-expressing neurons as well as infusing TRHR ligand into the MEA phenocopy functional manipulation of the COApm-MEA circuit. We have, therefore, uncovered a novel neural mechanism that endows animals with the ability to modulate innate reproductive and aggressive social interactions according to the health and threat status of reciprocating individuals. Deficits in such a mechanism may lead to the spread of disease, while uncontrolled engagement may lead to pathological conditions, such as social withdrawal and depression. To conduct circuit-based interrogation of COApm neurons projecting to MEAvGlut2+ neurons, we performed Translating Ribosome Affinity Purification (TRAP) using rabies viral tracing in the vGlut2-Cre mice.