A Neural Switch for Active and Passive Fear

• DOI: 10.1016/j.neuron.2010.07.008
• Publication Date: 2010-08-26T08:18:11Z
• Authors: Alessandro Gozzi; Apar Jain; Aldo Giovanelli; Cristina Bertollini; Valerio Crestan; Adam J. Schwarz; Theodoros Tsetsenis; Davide Ragozzino; Cornelius T. Gross; Angelo Bifone
• Keywords: Male; Neuroscience(all); Conditioning, Classical; Models, Neurological; Action Potentials; Mice, Transgenic; In Vitro Techniques; Mice; 03 medical and health sciences; 0302 clinical medicine; Adaptation, Psychological; Neural Pathways; Animals; Freezing Reaction, Cataleptic; Neurons; Blood Volume; fear behavior; amygdala; fMRI; cholinergic forebrain neurons; Brain; Fear; Amygdala; Magnetic Resonance Imaging; Mice, Inbred C57BL; Cerebrovascular Circulation; Mice, Inbred CBA

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.