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Cited by 209Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

A neural switch for active and passive fear

Open access
Gozzi, Alessandro, Jain, Apar, Giovanelli, Aldo, Bertollini, Cristina, Crestan, Valerio, Schwarz, Adam J., Tsetsenis, Theodoros, Ragozzino, Davide +2 more·2010·Neuron
DOI 10.1016/j.neuron.2010.07.008
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Abstract

The central nucleus of the amygdala (CeA) serves as a major output of this structure and plays a critical role in the expression of conditioned fear. By combining cell- and tissue-specific pharmacogenetic inhibition with functional magnetic resonance imaging (fMRI), we identified circuits downstream of CeA that control fear expression in mice. Selective inhibition of a subset of neurons in CeA led to decreased conditioned freezing behavior and increased cortical arousal as visualized by fMRI. Correlation analysis of fMRI signals identified functional connectivity between CeA, cholinergic forebrain nuclei, and activated cortical structures, and cortical arousal was blocked by cholinergic antagonists. Importantly, inhibition of these neurons switched behavioral responses to the fear stimulus from passive to active responses. Our findings identify a neural circuit in CeA that biases fear responses toward either passive or active coping strategies.

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Crossref · 10.1016/j.neuron.2010.07.008

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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.”

    From Freeze for action: neurobiological mechanisms in animal and human freezing (2017) · cites this paper as [41]

  • 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].”

    From Freeze for action: neurobiological mechanisms in animal and human freezing (2017) · cites this paper as [41]

  • The amygdala plays a key role in defensive behaviour and switching between defensive modes in rodents.

    “The amygdala plays a key role in defensive behaviour and switching between defensive modes in rodents [39–42].”

    From Freeze for action: neurobiological mechanisms in animal and human freezing (2017) · cites this paper as [41]

  • All defense responses in the animal model of the defense cascade-arousal, freezing, flight or fight, tonic immobility, collapsed immobility, and quiescent immobility-are responses to threat mediated by neural circuits involving the extended amygdala, hypothalamus, periaqueductal gray, ventral pontine tegmentum, ventral and dorsal medulla, and spinal cord.

    “All defense responses in the animal model of the defense cascade—arousal, freezing, flight or fight, tonic immobility, collapsed immobility, and quiescent immobility—are responses to threat mediated by neural circuits involving the extended amygdala, hypothalamus, periaqueductal gray (PAG), ventral pontine tegmentum, ventral and dorsal medulla, and spinal cord.22–25”

    From Fear and the Defense Cascade (2015) · cites this paper as [23]

  • The hippocampus, amygdala and PFC are critical nodes in adaptation and responses to stress.

    “the amygdala in mediating fear responses and the PFC in attention, these brain areas are critical nodes in adaptation and responses to stress (Belujon and Grace, 2011; Gozzi et al., 2010; McGaugh, 2004; Sapolsky, 2000; Tottenham and Sheridan, 2009).”

    From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Gozzi et al., 2010

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Authors
Gozzi, A., Jain, A., Giovanelli, A., Bertollini, C., Crestan, V., Schwarz, A. J., Tsetsenis, T., Ragozzino, D., Gross, C. T., & Bifone, A.
Affiliations
  • GlaxoSmithKline (Italy) (IT)
  • European Molecular Biology Laboratory (IT)
  • University of L'Aquila (IT)
  • Istituto Pasteur (IT)
  • Istituto Neurologico Mediterraneo (IT)
Corresponding author
Gross, Cornelius T.
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2010-08
Volume
67
Issue
4
Pages
656-666
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2010.07.008
OpenAlex
W2009342550
Cited by
209
References
41
Citations by year
2026: 5 · 2025: 4 · 2024: 9 · 2023: 14 · 2022: 10 · 2021: 11 · 2020: 16 · 2019: 17 · 2018: 14 · 2017: 16 · 2016: 14 · 2015: 12 · 2014: 16 · 2013: 16 · 2012: 17
FWCI
9.89
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
  • Archivio Istituzionale della Ricerca - Università degli Studi dell Aquila (submittedVersion)
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
central amygdala, fear conditioning, fear expression, cortical arousal, neural circuits, conditioned freezing, anticholinergic agents, functional connectivity
MeSH terms
Action Potentials, Adaptation, Psychological, Amygdala, Animals, Blood Volume, Brain, Cerebrovascular Circulation, Conditioning, Classical, Fear, Magnetic Resonance Imaging, Male, Mice, Inbred CBA, Mice, Inbred C57BL, Mice, Transgenic, Models, Neurological, Neural Pathways, Neurons, Oxytocin, Receptor, Serotonin, 5-HT1A, Freezing Reaction, Cataleptic, Mice, Serotonin 5-HT1 Receptor Agonists, Serotonin 5-HT1 Receptor Antagonists, In Vitro Techniques

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