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

David Terburg; Diego Scheggia; Rodrigo Triana Del Rio; Floris Klumpers; Alexandru Cristian Ciobanu; Barak Morgan; Estrella R Montoya; Peter A Bos; Gion Giobellina; Erwin H van den Burg; Beatrice de Gelder; Dan J Stein; Ron Stoop; Jack van Honk

doi:10.1016/j.cell.2018.09.028

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

Cell. 2018 Oct 18;175(3):723-735.e16. doi: 10.1016/j.cell.2018.09.028.

Affiliations

¹ Department of Psychology, Utrecht University, Utrecht, the Netherlands; Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa. Electronic address: d.terburg@uu.nl.
² Center for Psychiatric Neuroscience, Lausanne University and University Hospital Center, Lausanne, Switzerland.
³ Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
⁴ Global Risk Governance Program, Institute for Safety Governance and Criminology, Law Faculty, University of Cape Town, Cape Town, South Africa.
⁵ Department of Psychology, Utrecht University, Utrecht, the Netherlands.
⁶ Department of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands.
⁷ Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; MRC Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa.
⁸ Center for Psychiatric Neuroscience, Lausanne University and University Hospital Center, Lausanne, Switzerland. Electronic address: ron.stoop@unil.ch.
⁹ Department of Psychology, Utrecht University, Utrecht, the Netherlands; Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.

Abstract

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 (T_imm). In response to T_imm, 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, T_imm conditioning potentiated BLA projections onto an inhibitory CeA pathway, and pharmacological activation of this pathway rescued deficient T_imm 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.

Keywords: DREADD; Urbach Wiethe; basolateral amygdala; central amygdala; escape; fear; freezing; oxytocin; startle reflex; threat.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Animals
Basolateral Nuclear Complex / physiology*
Escape Reaction*
Fear
Female
Freezing Reaction, Cataleptic
Humans
Male
Rats
Rats, Sprague-Dawley
Reflex, Startle
Species Specificity

Grants and funding

CDP 13-004/HX/HSRD VA/United States