Cited by 1,786Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

Neuronal circuits for fear and anxiety

Tovote, Philip, Fadok, Jonathan Paul, Lüthi, Andreas·2015·Nature Reviews Neuroscience

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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Crossref · 10.1038/nrn3945

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195 of 195 references verified0 citation errors · 0 not checkable

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  • Flexibly shifting between freezing and active defensive modes relies on fronto-amygdala connections.

    “In addition, flexibly shifting between freezing and active defensive modes is critical for adequate stress-coping and relies on fronto-amygdala connections.”
  • Projections of the ventromedial prefrontal cortex and perigenual anterior cingulate cortex to the central nucleus of the amygdala facilitate rapid shifting between passive and active defence modes.

    “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].”
  • Humans, just like animals, recruit amygdala, periaqueductal grey and ventral forebrain structures to control the defence cascade.

    “These findings provide preliminary evidence that humans, just like animals, recruit amygdala, PAG and ventral forebrain structures to control the defence cascade [62].”
  • Enhanced amygdala responsivity is often associated with hyperactivity in a network that mediates anticipation of negative outcomes and hypoactivity in inhibitory systems involving ventromedial PFC.

    “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;”

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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
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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