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.

Psychedelics

“…Fear conditioning is known to be a model of emotional learning in which amygdala circuits play an important role (see references in Bombardi, 2014). The amygdala receives substantial serotoninergic innervation originating mainly from the dorsal raphe nucleus and, to a lesser extent, from the median raphe nucleus (Pralong et al, 2002;Hensler, 2006;Asan et al, 2013). Autoradiography with [ 3 H]ketanserin has shown light to moderate expression of 5-HT 2A receptors in most nuclei of the amygdala, with higher expression in the cortical nucleus and dorsolateral subdivision of the lateral nucleus .…”

IL-4 Knock Out Mice Display Anxiety-Like Behavior

“…Finally, anxiety is a complex neuropsychiatric disorder, where disturbed amygdala-based serotonin (5-HT) signaling is frequently cited as a mechanism (Asan et al 2013, Ousdal et al 2014). We found, however, that WT and IL-4 KO mice have similar basal neurotransmitter levels in the brain.…”

Effects of Escitalopram Administration on Face Processing in Intermittent Explosive Disorder: An fMRI Study

“…Therefore, in addition to dysfunctional amygdala-prefrontal circuitry (Coccaro et al, 2007), our findings suggest that the TPJ is also a potentially important brain region involved in IED and escitalopram may reduce aggressive tendencies toward others in IED by enhancing social-cognitive processing, rather than affecting the primary salience response of the amygdala. The amygdala is perhaps the most well-established region in face processing (Morris et al, 1998;Vuilleumier et al, 2001;Fusar-Poli et al, 2009) and a main target of dorsal raphe nucleus serotonergic projections (Maier et al, 2006;Asan et al, 2013). Previously, IED was found to be associated with a dysbalance in amygdala and OFC activity during threatening face processing (Coccaro et al, 2007).…”