TY - JOUR
T1 - Individual variability in behavior and functional networks predicts vulnerability using an animal model of PTSD
AU - Dopfel, David
AU - Perez, Pablo D.
AU - Verbitsky, Alexander
AU - Bravo-Rivera, Hector
AU - Ma, Yuncong
AU - Quirk, Gregory J.
AU - Zhang, Nanyin
N1 - Funding Information:
The present study was partially supported by National Institute of Neurological Disorders and Stroke Grant R01NS085200 (PI: Nanyin Zhang, Ph.D) and National Institute of Mental Health Grant R01MH098003 and RF1MH114224 (PI: Nanyin Zhang, Ph.D) and R37MH058883 (PI: Gregory Quirk).
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Only a minority of individuals experiencing trauma subsequently develop post-traumatic stress disorder (PTSD). However, whether differences in vulnerability to PTSD result from a predisposition or trauma exposure remains unclear. A major challenge in differentiating these possibilities is that clinical studies focus on individuals already exposed to trauma without pre-trauma conditions. Here, using the predator scent model of PTSD in rats and a longitudinal design, we measure pre-trauma brain-wide neural circuit functional connectivity, behavioral and corticosterone responses to trauma exposure, and post-trauma anxiety. Freezing during predator scent exposure correlates with functional connectivity in a set of neural circuits, indicating pre-existing circuit function can predispose animals to differential fearful responses to threats. Counterintuitively, rats with lower freezing show more avoidance of the predator scent, a prolonged corticosterone response, and higher anxiety long after exposure. This study provides a framework of pre-existing circuit function that determines threat responses, which might directly relate to PTSD-like behaviors.
AB - Only a minority of individuals experiencing trauma subsequently develop post-traumatic stress disorder (PTSD). However, whether differences in vulnerability to PTSD result from a predisposition or trauma exposure remains unclear. A major challenge in differentiating these possibilities is that clinical studies focus on individuals already exposed to trauma without pre-trauma conditions. Here, using the predator scent model of PTSD in rats and a longitudinal design, we measure pre-trauma brain-wide neural circuit functional connectivity, behavioral and corticosterone responses to trauma exposure, and post-trauma anxiety. Freezing during predator scent exposure correlates with functional connectivity in a set of neural circuits, indicating pre-existing circuit function can predispose animals to differential fearful responses to threats. Counterintuitively, rats with lower freezing show more avoidance of the predator scent, a prolonged corticosterone response, and higher anxiety long after exposure. This study provides a framework of pre-existing circuit function that determines threat responses, which might directly relate to PTSD-like behaviors.
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U2 - 10.1038/s41467-019-09926-z
DO - 10.1038/s41467-019-09926-z
M3 - Article
C2 - 31147546
AN - SCOPUS:85066492865
VL - 10
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 2372
ER -