ArticleMolecular psychiatry2017
Cannabinoid CB1 receptors in distinct circuits of the extended amygdala determine fear responsiveness to unpredictable threat.
Article in Molecular psychiatry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 70 citations in OpenAlex.
- Trial
- Cannabinoid modulation of central amygdala population dynamics during threat investigation.Nature communications · 2026Article
- Fear, anxiety, and the extended amygdala-absence of evidence for strict functional segregation.Social cognitive and affective neuroscience · 2026Article
- Genetic Tools in Rodents to Study Cannabinoid Functions.Current topics in behavioral neurosciences · 2026Review
- Circuit mechanisms governing endocannabinoid modulation of affective behaviour and stress adaptation.Nature reviews. Neuroscience · 2025Review
- Fear, anxiety, and the extended amygdala-bioRxiv : the preprint server for biology · 2025Article
- A Shared Threat-Anticipation Circuit Is Dynamically Engaged at Different Moments by Certain and Uncertain Threat.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- A shared threat-anticipation circuit is dynamically engaged at different moments by certain and uncertain threat.bioRxiv : the preprint server for biology · 2025Article
- Endocannabinoid-mediated regulation of depression in the ovBNST.Frontiers in neuroscience · 2025Article
- Adolescent social anxiety is associated with diminished discrimination of anticipated threat and safety in the bed nucleus of the stria terminalis.Journal of psychopathology and clinical science · 2025Article
- Sex Differences in Neural Circuits Underlying Fear Processing.Current topics in behavioral neurosciences · 2025Review
- Neuroticism/Negative Emotionality Is Associated with Increased Reactivity to Uncertain Threat in the Bed Nucleus of the Stria Terminalis, Not the Amygdala.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Neuroticism/negative emotionality is associated with increased reactivity to uncertain threat in the bed nucleus of the stria terminalis, not the amygdala.bioRxiv : the preprint server for biology · 2024Article
- Cannabinoid Type 1 Receptors in the Basolateral Amygdala Regulate ACPA-Induced Place Preference and Anxiolytic-Like Behaviors.Neurochemical research · 2022Article
- Interactions between the Nicotinic and Endocannabinoid Receptors at the Plasma Membrane.Membranes · 2022Review
- Increased cannabis intake during the COVID-19 pandemic is associated with worsening of depression symptoms in people with PTSD.BMC psychiatry · 2022Article
- Why Do Marijuana and Synthetic Cannabimimetics Induce Acute Myocardial Infarction in Healthy Young People?Cells · 2022Review
- Chronic Alcohol Dysregulates Glutamatergic Function in the Basolateral Amygdala in a Projection-and Sex-Specific Manner.Frontiers in cellular neuroscience · 2022Article
- Lateral hypothalamus involvement in control of stress response by bed nucleus of the stria terminalis endocannabinoid neurotransmission in male rats.Scientific reports · 2021Article
- Functional deletion of neuropeptide Y receptors type 2 in local synaptic networks of anteroventral BNST facilitates recall and increases return of fear.Molecular psychiatry · 2021Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The brain circuits underlying behavioral fear have been extensively studied over the last decades. Although the vast majority of experimental studies assess fear as a transient state of apprehension in response to a discrete threat, such phasic states of fear can shift to a sustained anxious apprehension, particularly in face of diffuse cues with unpredictable environmental contingencies. Unpredictability, in turn, is considered an important variable contributing to anxiety disorders. The networks of the extended amygdala have been suggested keys to the control of phasic and sustained states of fear, although the underlying synaptic pathways and mechanisms remain poorly understood. Here, we show that the endocannabinoid system acting in synaptic circuits of the extended amygdala can explain the fear response profile during exposure to unpredictable threat. Using fear training with predictable or unpredictable cues in mice, combined with local and cell-type-specific deficiency and rescue of cannabinoid type 1 (CB1) receptors, we found that presynaptic CB1 receptors on distinct amygdala projections to bed nucleus of the stria terminalis (BNST) are both necessary and sufficient for the shift from phasic to sustained fear in response to an unpredictable threat. These results thereby identify the causal role of a defined protein in a distinct brain pathway for the temporal development of a sustained state of anxious apprehension during unpredictability of environmental influences, reminiscent of anxiety symptoms in humans.
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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.