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

Research output: Contribution to journalArticleAcademicpeer-review

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 (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.

Original languageEnglish
Article numbere16
Pages (from-to)723-735
Number of pages29
JournalCell
Volume175
Issue number3
DOIs
Publication statusPublished - 18 Oct 2018

Keywords

  • CONDITIONED FEAR
  • THREAT
  • CIRCUIT
  • MAPS
  • ACTIVATIONS
  • AVOIDANCE
  • PATHWAYS
  • BEHAVIOR
  • ANXIETY
  • SYSTEM

Cite this

Terburg, D., Scheggia, D., Triana Del Rio, R., Klumpers, F., Ciobanu, A. C., Morgan, B., ... van Honk, J. (2018). The Basolateral Amygdala Is Essential for Rapid Escape: A Human and Rodent Study. Cell, 175(3), 723-735. [e16]. https://doi.org/10.1016/j.cell.2018.09.028
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. / The Basolateral Amygdala Is Essential for Rapid Escape : A Human and Rodent Study. In: Cell. 2018 ; Vol. 175, No. 3. pp. 723-735.
@article{76accc40f4c14bc39e2823c6dc823a60,
title = "The Basolateral Amygdala Is Essential for Rapid Escape: A Human and Rodent Study",
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 (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.",
keywords = "CONDITIONED FEAR, THREAT, CIRCUIT, MAPS, ACTIVATIONS, AVOIDANCE, PATHWAYS, BEHAVIOR, ANXIETY, SYSTEM",
author = "David Terburg and Diego Scheggia and {Triana Del Rio}, Rodrigo and Floris Klumpers and Ciobanu, {Alexandru Cristian} and Barak Morgan and Montoya, {Estrella R} and Bos, {Peter A} and Gion Giobellina and {van den Burg}, {Erwin H} and {de Gelder}, Beatrice and Stein, {Dan J} and Ron Stoop and {van Honk}, Jack",
note = "Copyright {\circledC} 2018 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2018",
month = "10",
day = "18",
doi = "10.1016/j.cell.2018.09.028",
language = "English",
volume = "175",
pages = "723--735",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "3",

}

Terburg, D, Scheggia, D, Triana Del Rio, R, Klumpers, F, Ciobanu, AC, Morgan, B, Montoya, ER, Bos, PA, Giobellina, G, van den Burg, EH, de Gelder, B, Stein, DJ, Stoop, R & van Honk, J 2018, 'The Basolateral Amygdala Is Essential for Rapid Escape: A Human and Rodent Study', Cell, vol. 175, no. 3, e16, pp. 723-735. https://doi.org/10.1016/j.cell.2018.09.028

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

In: Cell, Vol. 175, No. 3, e16, 18.10.2018, p. 723-735.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - The Basolateral Amygdala Is Essential for Rapid Escape

T2 - A Human and Rodent Study

AU - Terburg, David

AU - Scheggia, Diego

AU - Triana Del Rio, Rodrigo

AU - Klumpers, Floris

AU - Ciobanu, Alexandru Cristian

AU - Morgan, Barak

AU - Montoya, Estrella R

AU - Bos, Peter A

AU - Giobellina, Gion

AU - van den Burg, Erwin H

AU - de Gelder, Beatrice

AU - Stein, Dan J

AU - Stoop, Ron

AU - van Honk, Jack

N1 - Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2018/10/18

Y1 - 2018/10/18

N2 - 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.

AB - 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.

KW - CONDITIONED FEAR

KW - THREAT

KW - CIRCUIT

KW - MAPS

KW - ACTIVATIONS

KW - AVOIDANCE

KW - PATHWAYS

KW - BEHAVIOR

KW - ANXIETY

KW - SYSTEM

U2 - 10.1016/j.cell.2018.09.028

DO - 10.1016/j.cell.2018.09.028

M3 - Article

C2 - 30340041

VL - 175

SP - 723

EP - 735

JO - Cell

JF - Cell

SN - 0092-8674

IS - 3

M1 - e16

ER -

Terburg D, Scheggia D, Triana Del Rio R, Klumpers F, Ciobanu AC, Morgan B et al. The Basolateral Amygdala Is Essential for Rapid Escape: A Human and Rodent Study. Cell. 2018 Oct 18;175(3):723-735. e16. https://doi.org/10.1016/j.cell.2018.09.028