A neural switch for active and passive fear

Alessandro Gozzi; Apar Jain; Aldo Giovannelli; Cristina Bertollini; Valerio Crestan; Adam J Schwarz; Theodoros Tsetsenis; Davide Ragozzino; Cornelius T Gross; Angelo Bifone

doi:10.1016/j.neuron.2010.07.008

A neural switch for active and passive fear

Neuron. 2010 Aug 26;67(4):656-66. doi: 10.1016/j.neuron.2010.07.008.

Authors

Alessandro Gozzi¹, Apar Jain, Aldo Giovannelli, Cristina Bertollini, Valerio Crestan, Adam J Schwarz, Theodoros Tsetsenis, Davide Ragozzino, Cornelius T Gross, Angelo Bifone

Affiliation

¹ Neurosciences CEDD, GlaxoSmithKline Medicines Research Centre, via Fleming 4, 37135 Verona, Italy.

PMID: 20797541
DOI: 10.1016/j.neuron.2010.07.008

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Action Potentials / drug effects
Action Potentials / physiology
Adaptation, Psychological / drug effects
Adaptation, Psychological / physiology
Amygdala / blood supply
Amygdala / drug effects
Amygdala / physiology*
Animals
Blood Volume / drug effects
Brain / blood supply
Brain / drug effects
Brain / physiology*
Cerebrovascular Circulation / drug effects
Conditioning, Classical / drug effects
Conditioning, Classical / physiology
Fear / drug effects
Fear / physiology*
Freezing Reaction, Cataleptic / drug effects
Freezing Reaction, Cataleptic / physiology
In Vitro Techniques
Magnetic Resonance Imaging
Male
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Transgenic
Models, Neurological
Neural Pathways / blood supply
Neural Pathways / drug effects
Neural Pathways / physiology
Neurons / drug effects
Neurons / physiology*
Oxytocin / metabolism
Receptor, Serotonin, 5-HT1A / metabolism
Serotonin 5-HT1 Receptor Agonists
Serotonin 5-HT1 Receptor Antagonists

Substances

Serotonin 5-HT1 Receptor Agonists
Serotonin 5-HT1 Receptor Antagonists
Receptor, Serotonin, 5-HT1A
Oxytocin