@article{ref1,
title="High behavioral sensitivity to carbon dioxide associates with enhanced fear memory and altered forebrain neuronal activation",
journal="Neuroscience",
year="2020",
author="McMurray, Katherine M. J. and Gray, Alijah and Horn, Paul and Sah, Renu",
volume="ePub",
number="ePub",
pages="ePub-ePub",
abstract="There is considerable interest in pre-trauma individual differences that may contribute to increased risk for developing post-traumatic stress disorder (PTSD). Identification of underlying vulnerability factors that predict differential responses to traumatic experiences is important. Recently, the relevance of homeostatic perturbations in shaping long-term behavior has been recognized. Sensitivity to CO<sub>2</sub> inhalation, a homeostatic threat to survival, was shown to associate with the later development of PTSD symptoms in veterans. Here, we investigated whether behavioral sensitivity to CO<sub>2</sub> associates with PTSD-relevant behaviors and alters forebrain fear circuitry in mice. Mice were exposed to 5% CO<sub>2</sub> or air inhalation and tested one week later on acoustic startle and footshock contextual fear conditioning, extinction and reinstatement. CO<sub>2</sub> inhalation evoked heterogenous freezing behaviors (high freezing CO<sub>2</sub>-H and low freezing CO<sub>2</sub>-L) that significantly associated with fear conditioning and extinction behaviors. CO<sub>2</sub>-H mice elicited potentiated conditioned fear and delayed extinction while behavioral responses in CO<sub>2</sub>-L mice were similar to the air group. Persistent neuronal activation marker ΔFosB immunostaining revealed altered regional neuronal activation within the hippocampus, amygdala and medial pre-frontal cortex that correlated with conditioned fear and extinction. Inter-regional co-activation mapping revealed disruptions in the coordinated activity of hippocampal dentate-amygdala-infralimbic regions and infralimbic-prelimbic associations in CO<sub>2</sub>-H mice that may explain their enhanced fear phenotype. In conclusion, our data support an association of behavioral sensitivity to interoceptive threats such as CO<sub>2</sub> with altered fear responding to exteroceptive threats and suggest that &quot;CO<sub>2</sub>-sensitive&quot; individuals may be susceptible to developing PTSD.<br><br>Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.<p /> <p>Language: en</p>",
language="en",
issn="0306-4522",
doi="10.1016/j.neuroscience.2019.12.009",
url="http://dx.doi.org/10.1016/j.neuroscience.2019.12.009"
}