Serotonergic innervation of the amygdala: targets, receptors, and implications for stress and anxiety

Abstract

The amygdala is a core component of neural circuits that mediate processing of emotional, particularly anxiety and fear-related stimuli across species. In addition, the nuclear complex plays a key role in the central nervous system stress response, and alterations in amygdala responsivity are found in neuropsychiatric disorders, especially those precipitated or sustained by stressors. Serotonin has been shown to shape and fine-tune neural plasticity in development and adulthood, thereby allowing for network flexibility and adaptive capacity in response to environmental challenges, and is implicated in the modulation of stimulus processing and stress sensitivity in the amygdala. The fact that altered amygdala activity patterns are observed upon pharmacological manipulations of serotonergic transmission, as well as in carriers of genetic variations in serotonin pathway-associated signaling molecules representing risk factors for neuropsychiatric disorders, underlines the importance of understanding the role and mode of action of serotonergic transmission in the amygdala for human psychopathology. Here, we present a short overview over organizational principles of the amygdala in rodents, non-human primates and humans, and review findings on the origin, morphology, and targets of serotonergic innervation, the distribution patterns and cellular expression of serotonin receptors, and the consequences of stress and pharmacological manipulations of serotonergic transmission in the amygdala, focusing particularly on the extensively studied basolateral complex and central nucleus.