Conditioned emotional responses are generated by the actions of the hippocampus and septum on the amygdala, which induces physiological change through its midbrain projections. An emotional response to a social threat involves the appropriate sensory cortices, frontal cortex, hippocampus and septum, midbrain, and hypothalamus. The affective experience of abandonment can be followed by the separation distress sequence of protest and despair or it can initiate shame. Shame recruits circuits formed for hiding from physical danger for avoidant responses to the failure of social belonging. Attachment typically begins in the mother-infant dyad but broadens to promote and reward inclusion in a larger social group as the individual grows. The social attachments, fears of ostracism, and feelings of distress at loss of inclusion have their neurobiological bases in brain systems designed to ensure healthy attachment, learning of emotion regulation, and development of socialized behaviors, from infancy onwards.