The Basolateral Amygdala Is Essential for Rapid Escape: A Human and Rodent Study

Rodent research delineates how the basolateral amygdala (BLA) and central amygdala (CeA) control defensive behaviors, but translation of these findings to humans is needed. Here, we compare humans with natural-selective bilateral BLA lesions to rats with a chemogenetically silenced BLA. We find, acr...

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Bibliographic Details
Published in:Cell 2018-10, Vol.175 (3), p.723-735.e16
Main Authors: Terburg, David, Scheggia, Diego, Triana del Rio, Rodrigo, Klumpers, Floris, Ciobanu, Alexandru Cristian, Morgan, Barak, Montoya, Estrella R., Bos, Peter A., Giobellina, Gion, van den Burg, Erwin H., de Gelder, Beatrice, Stein, Dan J., Stoop, Ron, van Honk, Jack
Format: Article
Language:English
Subjects:
Adult
Animals
basolateral amygdala
Basolateral Nuclear Complex - physiology
central amygdala
DREADD
escape
Escape Reaction
Fear
Female
freezing
Freezing Reaction, Cataleptic
Humans
Male
oxytocin
Rats
Rats, Sprague-Dawley
Reflex, Startle
Species Specificity
startle reflex
threat
Urbach Wiethe
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Summary:Rodent research delineates how the basolateral amygdala (BLA) and central amygdala (CeA) control defensive behaviors, but translation of these findings to humans is needed. Here, we compare humans with natural-selective bilateral BLA lesions to rats with a chemogenetically silenced BLA. We find, across species, an essential role for the BLA in the selection of active escape over passive freezing during exposure to imminent yet escapable threat (Timm). In response to Timm, BLA-damaged humans showed increased startle potentiation and BLA-silenced rats demonstrated increased startle potentiation, freezing, and reduced escape behavior as compared to controls. Neuroimaging in humans suggested that the BLA reduces passive defensive responses by inhibiting the brainstem via the CeA. Indeed, Timm conditioning potentiated BLA projections onto an inhibitory CeA pathway, and pharmacological activation of this pathway rescued deficient Timm responses in BLA-silenced rats. Our data reveal how the BLA, via the CeA, adaptively regulates escape behavior from imminent threat and that this mechanism is evolutionary conserved across rodents and humans. [Display omitted] •Human bilateral BLA damage and silencing in rats results in maladaptive passive fear•If active escape is feasible, the BLA prevents passive freezing responses via the CeA•BLA action on an inhibitory CeA pathway permits the adaptive shift to active escape•Activation of CeA neurons by oxytocin rescues deficient escape in BLA-silenced rats Under conditions of imminent threat, by activating an inhibitory central amygdala pathway, the rodent and human basolateral amygdala play a key role in adaptively selecting and executing active escape responses rather than passive freezing behaviors.
ISSN:0092-8674
1097-4172
1097-4172
DOI:10.1016/j.cell.2018.09.028