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Neuron. 2019 Aug 7;103(3):489-505.e7. doi: 10.1016/j.neuron.2019.05.029. Epub 2019 Jun 13.

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

Author information

1
Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, USA. Electronic address: ayesha.sengupta@nih.gov.
2
Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, USA. Electronic address: holmesan@mail.nih.gov.

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.

KEYWORDS:

5-HT; basal amygdala; dorsal raphe nucleus; fear conditioning; fear extinction; nucleus accumbens; serotonin

PMID:
31204082
PMCID:
PMC6687558
[Available on 2020-08-07]
DOI:
10.1016/j.neuron.2019.05.029

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