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

Abstract

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^SST+ 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^SST+ 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^SST+ 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.