TY - JOUR
T1 - Longitudinal assessment of amygdala activity in mice susceptible to trauma
AU - Dirven, Bart C.J.
AU - Botan, Andriana
AU - van der Geugten, Dewi
AU - Kraakman, Blom
AU - van Melis, Lennart
AU - Merjenburgh, Sanne
AU - van Rijn, Rebecca
AU - Waajen, Liz
AU - Homberg, Judith R.
AU - Kozicz, Tamas
AU - Henckens, Marloes J.A.G.
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/11
Y1 - 2022/11
N2 - Resilience to consequences of trauma exposure contains relevant information about the processes that contribute to the maintenance of mental health in the face of adversity; information that is essential to improve treatment success of stress-related mental diseases. Prior literature has implicated aberrant amygdala (re)activity as potential factor contributing to trauma susceptibility. However, it remains to be resolved which amygdalar subregions and neuronal subclasses are involved, and when – i.e., pre-, peri- or post-trauma exposure – and under what conditions changes in amygdala (re)activity manifest themselves. Here, we implemented a preclinical rodent model for PTSD that entailed exposure to a traumatic event (severe, unpredictable foot shock) followed by a trigger (mild, predictable foot shock). Using behavioral phenotyping, trauma susceptible vs. resilient mice were identified and pre-, peri- or post-trauma amygdala activity was compared. Neuronal activity was tagged in living mice by the use of the ArcTRAP transgenic mouse line, labeling all activated (i.e., Arc-expressing) neurons by a systemic injection of tamoxifen. Furthermore, we assessed amygdala responses during fear memory recall, induced by either (re-)exposure to the trauma, trigger, or a novel, yet similar context, and analyzed behavioral fear responses under these conditions, as well as basal anxiety in the mice. Results revealed no major differences dissociating susceptible vs. resilient mice prior to trauma exposure, but exaggerated activity in specifically the basolateral amygdala (BLA) peri-trauma that predicted susceptibility to later PTSD-like symptoms. Post-trauma, susceptible mice did not display altered basal amygdala activity, but BLA hyperreactivity in response to trigger context re-exposure, and BLA hyporesponsivity in response to the trauma context. Exposure to the novel, similar context evoked a differential temporal pattern of freezing behavior in susceptible mice and an increased activity of amygdalar somatostatin-expressing neurons specifically. As such, these results for the first time show that deviant BLA activity during fear learning predicts susceptibility to its long-term consequences and that aberrant subsequent BLA responses to stressful contexts depend on the exact context.
AB - Resilience to consequences of trauma exposure contains relevant information about the processes that contribute to the maintenance of mental health in the face of adversity; information that is essential to improve treatment success of stress-related mental diseases. Prior literature has implicated aberrant amygdala (re)activity as potential factor contributing to trauma susceptibility. However, it remains to be resolved which amygdalar subregions and neuronal subclasses are involved, and when – i.e., pre-, peri- or post-trauma exposure – and under what conditions changes in amygdala (re)activity manifest themselves. Here, we implemented a preclinical rodent model for PTSD that entailed exposure to a traumatic event (severe, unpredictable foot shock) followed by a trigger (mild, predictable foot shock). Using behavioral phenotyping, trauma susceptible vs. resilient mice were identified and pre-, peri- or post-trauma amygdala activity was compared. Neuronal activity was tagged in living mice by the use of the ArcTRAP transgenic mouse line, labeling all activated (i.e., Arc-expressing) neurons by a systemic injection of tamoxifen. Furthermore, we assessed amygdala responses during fear memory recall, induced by either (re-)exposure to the trauma, trigger, or a novel, yet similar context, and analyzed behavioral fear responses under these conditions, as well as basal anxiety in the mice. Results revealed no major differences dissociating susceptible vs. resilient mice prior to trauma exposure, but exaggerated activity in specifically the basolateral amygdala (BLA) peri-trauma that predicted susceptibility to later PTSD-like symptoms. Post-trauma, susceptible mice did not display altered basal amygdala activity, but BLA hyperreactivity in response to trigger context re-exposure, and BLA hyporesponsivity in response to the trauma context. Exposure to the novel, similar context evoked a differential temporal pattern of freezing behavior in susceptible mice and an increased activity of amygdalar somatostatin-expressing neurons specifically. As such, these results for the first time show that deviant BLA activity during fear learning predicts susceptibility to its long-term consequences and that aberrant subsequent BLA responses to stressful contexts depend on the exact context.
KW - Amygdala
KW - Mouse model
KW - Neuronal activity
KW - PTSD
KW - Resilience
KW - Trauma
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UR - http://www.scopus.com/inward/citedby.url?scp=85138833993&partnerID=8YFLogxK
U2 - 10.1016/j.psyneuen.2022.105912
DO - 10.1016/j.psyneuen.2022.105912
M3 - Article
C2 - 36113379
AN - SCOPUS:85138833993
SN - 0306-4530
VL - 145
JO - Psychoneuroendocrinology
JF - Psychoneuroendocrinology
M1 - 105912
ER -