A competitive inhibitory circuit for selection of active and passive fear responses
Nature. 2017-01-25; 542(7639): 96-100
DOI: 10.1038/nature21047
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Fadok JP(1), Krabbe S(1), Markovic M(1)(2), Courtin J(1), Xu C(1), Massi L(1), Botta P(1)(2), Bylund K(1), Müller C(1), Kovacevic A(1), Tovote P(1), Lüthi A(1)(2).
Author information:
(1)Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
(2)University of Basel, 4000 Basel, Switzerland.
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.