Activation of somatostatin neurons in the medial amygdala reverses long-term aggression and social deficits associated to early-life stress in male mice

Early postnatal development is a critical period for the configuration of neural networks that support social and affective-like behaviors. In this sense, children raised in stressful environments are at high risk to develop maladaptive behaviors immediately or later in life, including anti-social and aggressive behaviors. However, the neurobiological bases of such phenomena remain poorly understood. Here we showed that, at long-term, maternal separation with early weaning (MSEW) decreased the density of somatostatin-expressing (SST+) neurons in the basolateral amygdala (BLA) of females and males, while their activity was only reduced in the medial amygdala (MeA) of males. Interestingly, only MSEW males exhibited long-term behavioral effects, including reduced sociability and social novelty preference in the 3-chamber test (3CH), decreased social interest in the resident-intruder test (RI), and increased aggressivity in both the RI and the tube dominance test (TT). To test whether the manipulation of MeA neurons was sufficient to reverse these negative behavioral outcomes, we expressed the chemogenetic excitatory receptor hM3Dq in MSEW adult males. We found that the activation of MeA neurons ameliorated social interest in the RI test and reduced aggression traits in the TT and RI assays. Altogether, our results highlight a role for MeA neurons in the regulation of aggressivity and social interest and point to the loss of activity of these neurons as a plausible etiological mechanism linking early life stress to these maladaptive behaviors in later life.