A Discrete Dorsal Raphe to Basal Amygdala 5-HT Circuit Calibrates Aversive Memory.

ABSTRACT: Despite a wealth of clinical and preclinical data implicating the serotonin (5-HT) system in fear-related affective disorders, a precise definition of this neuromodulator's role in fear remains elusive. Using convergent anatomical and functional approaches, we interrogate the contribution to fear of basal amygdala (BA) 5-HT inputs from the dorsal raphe nucleus (DRN). We show the DRN?BA 5-HT pathway is engaged during fear memory formation and retrieval, and activity of these projections facilitates fear and impairs extinction. The DRN?BA 5-HT pathway amplifies fear-associated BA neuronal firing and theta power and phase-locking. Although fear recruits 5-HT and VGluT3 co-expressing DRN neurons, the fear-potentiating influence of the DRN?BA 5-HT pathway requires signaling at BA 5-HT1A/2A receptors. Input-output mapping illustrates how the DRN?BA 5-HT pathway is anatomically distinct and connected with other brain regions that mediate fear. These findings reveal how a discrete 5-HT circuit orchestrates a broader neural network to calibrate aversive memory.

SUBMITTER: Sengupta A 

PROVIDER: S-EPMC6687558 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature