Internal medicine

Neuroscience

Receptor

Serotonin

Central nucleus of the amygdala

Nucleus

Serotonergic

Central nervous system

Psychology

Raphe nuclei

Functional magnetic resonance imaging

Habenula

Chronic pain

Amygdala

Thalamus

Dorsal raphe nucleus

Optogenetics

Medicine

Nature Neuroscience

Comorbid depressive symptoms (CDS) in chronic pain are a common health problem, but the neural circuit mechanisms underlying these symptoms remain unclear. Here we identify a novel pathway involving 5-hydroxytryptamine (5-HT) projections from the dorsal raphe nucleus (5-HTDRN) to somatostatin (SOM)-expressing and non-SOM interneurons in the central nucleus of the amygdala (CeA). The SOMCeA neurons project directly to the lateral habenula, an area known involved in depression. Inhibition of the 5-HTDRN→SOMCeA pathway produced depression-like behavior in a male mouse model of chronic pain. Activation of this pathway using pharmacological or optogenetic approaches reduced depression-like behavior in these mice. Human functional magnetic resonance imaging data showed that compared to healthy controls, functional connectivity between the CeA-containing centromedial amygdala and the DRN was reduced in patients with CDS but not in patients in chronic pain without depression. These findings indicate that a novel 5-HTDRN→SOMCeA→lateral habenula pathway may mediate at least some aspects of CDS. Zhou et al. report a novel 5-HT circuit from the dorsal raphe nucleus to somatostatin-expressing neurons in the central nucleus of the amygdala that partially mediates depressive-like behavior in a mouse model of chronic pain.

A neural circuit for comorbid depressive symptoms in chronic pain