ArticleProceedings of the National Academy of Sciences of the United States of America2013
Orexin/hypocretin system modulates amygdala-dependent threat learning through the locus coeruleus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
101 citing papers in PubMed, 192 citations in OpenAlex.
- Alpha-2 Adrenoreceptor Antagonist Yohimbine Potentiates Consolidation of Conditioned Fear.The international journal of neuropsychopharmacology · 2022Trial
- Locus-Coeruleus Norepinephrine Functioning as a Predictor of Childhood Mental Health (LOCUS-MENTAL): Protocol for a Longitudinal Study.JMIR research protocols · 2026Article
- Social defeat stress responses in the stress alternative model are dependent on sex and anterior basolateral amygdala orexin 2 receptors.Biology of sex differences · 2026Article
- Review
- Repeated Morphine Exposure Reversibly Impairs Spike Generation and Repetitive Firing in a Functionally Distinct Subpopulation of Orexin Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- The orexin/hypocretin system in dementia-related neurological disorders: a double-edged sword in cognitive impairment.Psychopharmacology · 2025Review
- Orexin and Lifestyle Habits: A Meaningful Connection Among Nutrition, Physical Activity, and Sleep Pattern in Health and Diseases.International journal of molecular sciences · 2025Review
- Neuropeptides as transmitters and regulators of the locus coeruleus noradrenergic system.Pharmacological reviews · 2025Review
- Associations of COPhysiology & behavior · 2025Article
- Orexin receptors: possible therapeutic targets for psychiatric disorders.Psychopharmacology · 2025Review
- Hypothalamic Control of Learned Flight Induced by Threat Imminence.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Orexin mechanisms in the prelimbic cortex modulate the expression of contextual conditioned fear.Psychopharmacology · 2025Article
- Monosynaptic ventral tegmental area glutamate projections to the locus coeruleus enhance aversive processing.bioRxiv : the preprint server for biology · 2024Article
- The Aggravating Role of Failing Neuropeptide Networks in the Development of Sporadic Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Interaction between corticotropin-releasing factor, orexin, and dynorphin in the infralimbic cortex may mediate exacerbated alcohol-seeking behavior.Neurobiology of stress · 2024Article
- Review
- Fear attenuation collaborations to optimize translation.Behavioral neuroscience · 2024Article
- Orexins and primary headaches: an overview of the neurobiology and clinical impact.Expert review of neurotherapeutics · 2024Review
- Article
- The Orexin/Hypocretin System, the Peptidergic Regulator of Vigilance, Orchestrates Adaptation to Stress.Biomedicines · 2024Review
41 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Survival in a dangerous environment requires learning about stimuli that predict harm. Although recent work has focused on the amygdala as the locus of aversive memory formation, the hypothalamus has long been implicated in emotional regulation, and the hypothalamic neuropeptide orexin (hypocretin) is involved in anxiety states and arousal. Nevertheless, little is known about the role of orexin in aversive memory formation. Using a combination of behavioral pharmacology, slice physiology, and optogenetic techniques, we show that orexin acts upstream of the amygdala via the noradrenergic locus coeruleus to enable threat (fear) learning, specifically during the aversive event. Our results are consistent with clinical studies linking orexin levels to aversive learning and anxiety in humans and dysregulation of the orexin system may contribute to the etiology of fear and anxiety disorders.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.