Activation of somatostatin interneurons in the medial amygdala reverses long-term aggressive behavior associated to early-life stress in male mice

Abstract

Abstract Early postnatal development is a critical period for the configuration of neural networks that support emotional and socio-affective behaviors. In this sense, children raised in stressful environments are at high risk of developing 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 (SST) interneurons in the basolateral amygdala (BLA) of females and males, while their activity was only reduced in the medial amygdala (MeA) of males. Interestingly, this hypoactivity resulted in increased aggressivity and low social interest. To test whether the manipulation of MeASST+ interneurons was sufficient to reverse these negative behavioral outcomes, we chemogenetically expressed hM3Dq receptors in MSEW adult males. We found that the activation of MeASST+ interneurons ameliorated social interaction and reduced aggression traits. Altogether, our results highlight a role for MeASST+ 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.