title: A competitive inhibitory circuit for selection of active and passive fear responses.
abstract: When faced with threat, the survival of an organism is contingent upon the selection of appropriate active or passive behavioural responses. Freezing is an evolutionarily conserved passive fear response that has been used extensively to study the neuronal mechanisms of fear and fear conditioning in rodents. However, rodents also exhibit active responses such as flight under natural conditions. The central amygdala (CEA) is a forebrain structure vital for the acquisition and expression of conditioned fear responses, and the role of specific neuronal sub-populations of the CEA in freezing behaviour is well-established. Whether the CEA is also involved in flight behaviour, and how neuronal circuits for active and passive fear behaviour interact within the CEA, are not yet understood. Here, using in vivo optogenetics and extracellular recordings of identified cell types in a behavioural model in which mice switch between conditioned freezing and flight, we show that active and passive fear responses are mediated by distinct and mutually inhibitory CEA neurons. Cells expressing corticotropin-releasing factor (CRF+) mediate conditioned flight, and activation of somatostatin-positive (SOM+) neurons initiates passive freezing behaviour. Moreover, we find that the balance between conditioned flight and freezing behaviour is regulated by means of local inhibitory connections between CRF+and SOM+neurons, indicating that the selection of appropriate behavioural responses to threat is based on competitive interactions between two defined populations of inhibitory neurons, a circuit motif allowing for rapid and flexible action selection.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Fadok
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Krabbe
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.|University of Basel, 4000 Basel, Switzerland.
authors.forename: Milica
authors.initials: M
authors.lastname: Markovic
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Julien
authors.initials: J
authors.lastname: Courtin
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Chun
authors.initials: C
authors.lastname: Xu
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Lema
authors.initials: L
authors.lastname: Massi
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.|University of Basel, 4000 Basel, Switzerland.
authors.forename: Paolo
authors.initials: P
authors.lastname: Botta
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Kristine
authors.initials: K
authors.lastname: Bylund
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Müller
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Kovacevic
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Philip
authors.initials: P
authors.lastname: Tovote
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.|University of Basel, 4000 Basel, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lüthi
mesh_terms: D000818:Animals; D066274:Central Amygdaloid Nucleus / Q000166:cytology / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004924:Escape Reaction / Q000502:physiology*; D005239:Fear / Q000502:physiology* / Q000523:psychology*; D046352:Freezing Reaction, Cataleptic / Q000502:physiology*; D008124:Locomotion / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008959:Models, Neurological; D009433:Neural Inhibition; D009434:Neural Pathways; D009474:Neurons / Q000502:physiology*; D062308:Optogenetics; D013004:Somatostatin / Q000378:metabolism
chemical_list: D013004:Somatostatin; D003346:Corticotropin-Releasing Hormone