ArticleJournal of psychopharmacology (Oxford, England)2020
Using loss- and gain-of-function approaches to target amygdala-projecting serotonergic neurons in the dorsal raphe nucleus that enhance anxiety-related and conditioned fear behaviors.
Article in Journal of psychopharmacology (Oxford, England), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- Behavioral impact of chemogenetic manipulations of 5-HT DRN neurons in transgenic Tph2-iCre rats.Psychopharmacology · 2026Article
- Neurobiological correlates of behavioral resilience to chronic alcohol and acute stress in male and female rats.Translational psychiatry · 2026Article
- Sleep and stress as modifiable drivers of Alzheimer's disease.NPJ dementia · 2026Review
- Role of serotonin neurons in the dorsal raphe nucleus in heroin self-administration and punishment.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Disfunction of dorsal raphe nucleus-hippocampus serotonergic-HTR3 transmission results in anxiety phenotype of Neuroplastin 65-deficient mice.Acta pharmacologica Sinica · 2024Article
- Identification of a novel perifornical-hypothalamic-area-projecting serotonergic system that inhibits innate panic and conditioned fear responses.Translational psychiatry · 2024Article
- Chemogenetics drives paradigm change in the investigation of behavioral circuits and neural mechanisms underlying drug action.Behavioural brain research · 2021Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThe central serotonergic system originating from the dorsal raphe nucleus (DR) plays a critical role in anxiety and trauma-related disorders such as posttraumatic stress disorder. Although many studies have investigated the role of serotonin (5-HT) within pro-fear brain regions such as the amygdala, the majority of these studies have utilized non-selective pharmacological approaches or poorly understood lesioning techniques which limit their interpretation.
aimHere we investigated the role of amygdala-projecting 5-HT neurons in the DR in innate anxiety and conditioned fear behaviors.
methodsTo achieve this goal, we utilized (1) selective lesion of 5-HT neurons projecting to the amygdala with saporin toxin conjugated to anti-serotonin transporter (SERT) injected into the amygdala, and (2) optogenetic excitation of amygdala-projecting DR cell bodies with a combination of a retrogradely transported canine adenovirus-expressing Cre-recombinase injected into the amygdala and a Cre-dependent-channelrhodopsin injected into the DR.
resultsWhile saporin treatment lesioned both local amygdalar 5-HT fibers and neurons in the DR as well as reduced conditioned fear behavior, optical activation of amygdala-projecting DR neurons enhanced anxious behavior and conditioned fear response.
conclusionCollectively, these studies support the hypothesis that amygdala-projecting 5-HT neurons in the DR represent an anxiety and fear-on network.
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