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Neuronal circuits for fear and anxiety
Abstract
Decades of research has identified the brain areas that are involved in fear, fear extinction, anxiety and related defensive behaviours. Newly developed genetic and viral tools, optogenetics and advanced in vivo imaging techniques have now made it possible to characterize the activity, connectivity and function of specific cell types within complex neuronal circuits. Recent findings that have been made using these tools and techniques have provided mechanistic insights into the exquisite organization of the circuitry underlying internal defensive states. This Review focuses on studies that have used circuit-based approaches to gain a more detailed, and also more comprehensive and integrated, view on how the brain governs fear and anxiety and how it orchestrates adaptive defensive behaviours.
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“In addition, flexibly shifting between freezing and active defensive modes is critical for adequate stress-coping and relies on fronto-amygdala connections.”
From Freeze for action: neurobiological mechanisms in animal and human freezing (2017) · cites this paper as [62]
In the citing paper
“Projections of the ventromedial prefrontal cortex (vmPFC) and the perigenual anterior cingulate cortex (ACC) in particular to the CE of the amygdala in turn facilitate rapid shifting between passive and active defence modes [41,62].”
From Freeze for action: neurobiological mechanisms in animal and human freezing (2017) · cites this paper as [62]
In the citing paper
“These findings provide preliminary evidence that humans, just like animals, recruit amygdala, PAG and ventral forebrain structures to control the defence cascade [62].”
From Freeze for action: neurobiological mechanisms in animal and human freezing (2017) · cites this paper as [62]
In the citing paper
“Enhanced amygdala responsivity is often associated with hyperactivity in a network that mediates the anticipation of negative outcomes and consists of the anterior cingulate cortex, insula, dorsolateral PFC and the medial orbitofrontal cortex, and hypoactivity in inhibitory systems, for example involving the ventromedial PFC, which is implicated in top-down inhibition of amygdala output [Fig.3;”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Tovote et al., 2015
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Metadata
- Authors
- Tovote, P., Fadok, J. P., & Lüthi, A.
- Affiliations
- Friedrich Miescher Institute (CH)
- Corresponding author
- Lüthi, Andreas
- Venue
- Nature Reviews Neuroscience
- Published
- 2015-05-20
- Volume
- 16
- Issue
- 6
- Pages
- 317-331
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- OpenAlex
- W1547865271
- Semantic Scholar
- c2361b90aa8185adfda7e7329fc00f24a5a64602
- Cited by
- 1,786
- References
- 195
- Citations by year
- 2026: 141 · 2025: 174 · 2024: 188 · 2023: 184 · 2022: 186 · 2021: 176 · 2020: 173 · 2019: 154 · 2018: 163 · 2017: 123 · 2016: 103 · 2015: 21
- FWCI
- 13.59
- Type
- journal article
- Language
- en
- Update notices
- erratum (2015-06-10)
- Open access
- closed
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Brain Research Foundation
- Novartis Foundation
- National Alliance for Research on Schizophrenia and Depression
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- fear, anxiety, neural circuits, fear extinction, defensive behavior, neuronal connectivity, optogenetics, in vivo imaging, genetic instruments
- MeSH terms
- Animals, Anxiety, Brain, Fear, Humans, Neural Pathways
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