title: A neural switch for active and passive fear.
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.
authors.affiliation: Neurosciences CEDD, GlaxoSmithKline Medicines Research Centre, via Fleming 4, 37135 Verona, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gozzi
authors.forename: Apar
authors.initials: A
authors.lastname: Jain
authors.forename: Aldo
authors.initials: A
authors.lastname: Giovannelli
authors.forename: Aldo
authors.initials: A
authors.lastname: Giovanelli
authors.forename: Cristina
authors.initials: C
authors.lastname: Bertollini
authors.forename: Valerio
authors.initials: V
authors.lastname: Crestan
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Schwarz
authors.forename: Theodoros
authors.initials: T
authors.lastname: Tsetsenis
authors.forename: Davide
authors.initials: D
authors.lastname: Ragozzino
authors.forename: Cornelius T
authors.initials: CT
authors.lastname: Gross
authors.forename: Angelo
authors.initials: A
authors.lastname: Bifone
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000223:Adaptation, Psychological / Q000187:drug effects / Q000502:physiology; D000679:Amygdala / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001810:Blood Volume / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D008959:Models, Neurological; D009434:Neural Pathways / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010121:Oxytocin / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists
chemical_list: D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D010121:Oxytocin