Susceptibility and Resilience to PTSD-Like Symptoms in Mice Are Associated with Opposite Dendritic Changes in the Prelimbic and Infralimbic Cortices Following Trauma

doi:10.1016/j.neuroscience.2019.08.018

Neuroscience

Volume 418, 15 October 2019, Pages 166-176

https://doi.org/10.1016/j.neuroscience.2019.08.018 Get rights and content

Highlights

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Like humans, PTSD-like symptoms develop in some laboratory rodents, while others express less or no symptoms.
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Here, we found that trauma-exposure induces not only prefrontal changes in susceptible but also in resilient individuals.
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The type of post-trauma morphological changes in the mPFC is associated with susceptibility or resilience to PTSD-like symptoms.

Abstract

Post-traumatic stress disorder (PTSD) is triggered by exposure to traumatic events, but not everyone who experiences trauma develops this disorder. Like humans, PTSD-like symptoms develop in some laboratory rodents (susceptible individuals), while others express less or no symptoms (resilient individuals). Here, considering (i) the putative causal role of fear conditioning in PTSD development and (ii) the involvement of the medial prefrontal cortex (mPFC) in the regulation of conditioned fear response, we tested whether trauma-associated changes in the mPFC may discriminate stress-resilient from stress-susceptible mice. From data on avoidance behavior (as a major symptom), we found that trauma-exposed mice displayed a bimodal distribution in their step-through latency, with low avoider (stress-resilient) individuals and high avoider (stress-susceptible) individuals. Dendrites of Golgi–Cox-stained neurons were analyzed in two parts of the mPFC: the prelimbic (PrL) and infralimbic (IL) areas. In the resilient phenotype, the total number of dendrites decreased in the PrL and increased in the IL; however, it decreased only in the IL in the susceptible phenotype compared to controls. These findings demonstrate that the type of post-trauma morphological changes in the mPFC is associated with susceptibility or resilience to trauma-related symptoms.

Section snippets

INTRODUCTION

Post-traumatic stress disorder (PTSD) is a debilitating disorder that occurs after being exposed to one or multiple traumatic events. Clinical studies have highlighted that only a minority of trauma-exposed individuals develop PTSD (Kessler et al., 1995, Chilcoat and Breslau, 1998, Breslau and Kessler, 2001). Like humans, laboratory mice (Lebow et al., 2012, Sillivan et al., 2017) and rats (Elharrar et al., 2013, Toledano and Gisquet-Verrier, 2014) also display a great heterogeneity in their

Animals

The experiments were performed on 47 young male Swiss mice obtained from the animal care facility of the faculty of Science Semlalia, Marrakech, Morocco. Animals were group housed (3–6 per cage) and maintained under constant conditions of ambient temperature (22 ± 2 °C), under a 12 h light/12 h dark cycle with food and water available Ad libitum. The behavioral experiments were conducted between 8 AM and 3 PM in conformity with approved institutional protocols. All animal procedures were in

Labeling of mice as stress-susceptible or stress-resilient

All trauma-exposed mice acquired avoidance behavior, which was characterized by increases of step-through latency (Fig. 2A: Shocked group). Unpaired t-test revealed a significant difference between the Control and Shocked groups (t = 2.70, P = .009). After examining the frequency distribution of step-through latency time of mice (Fig. 2B), we found that the Control group showed a unimodal distribution while trauma-exposed mice showed a high variability with bimodal distribution (bimodal

DISCUSSION

In this study, we examined whether trauma exposure would cause opposite changes in the mPFC of mice that develop at least 3 PTSD-like symptoms (stress-susceptible group) and those developing less symptoms (stress-resilient group). To this end, a reliable evaluation method was used to allow the differentiation of trauma-exposed mice into susceptible and resilient groups. The Golgi-Cox method revealed significant decreases and increases in the total number of dendrites in the PrL and IL,

Authors' contributions

A.L., Y.B., M.B., S.B.M., and R.G. conceived and designed the study.

A.L. and Y.B. acquired the data.

A.L. analyzed the data.

A.L., S.B.M. and R.G. drafted the article.

All authors interpreted the data, discussed the results, and commented on the article.

Funding

This work was supported by a Marie Curie International Research Staff Exchange Scheme Fellowship within the 7th European Community Framework Programme (PIRSES-GA-2012-318997).

Notes

We acknowledge the support of the Centre National de la Recherche Scientifique et Technique (CNRST) of Morocco and the Université Cadi Ayyad in Marrakech.

Declaration of competing interest

None declared.

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Citation Excerpt :
The latter neuronal features are characterized by strong plasticity, particularly during the early stages of development of the nervous system. With regards to neuroadaptive cellular modifications influencing behavioral phenotypes, it has been reported that the dendritic harborization of limbic cortical neurons undergoes opposite changes, depending on whether the mouse phenotype will be susceptible or resilient to depression (Lguensat et al., 2019). VTA DA neurons are no exception to this, as it has been recently reported that maternal separation causes dendritic spine heads modifications (Spyrka et al., 2020).
Exposure to aversive events during sensitive developmental periods can affect the preferential coping strategy adopted by individuals later in life, leading to either stress-related psychiatric disorders, including depression, or to well-adaptation to future adversity and sources of stress, a behavior phenotype termed “resilience”.
We have previously shown that interfering with the development of mother-pups bond with the Repeated Cross Fostering (RCF) stress protocol can induce resilience to depression-like phenotype in adult C57BL/6J female mice. Here, we used patch-clamp recording in midbrain slice combined with both in vivo and ex vivo pharmacology to test our hypothesis of a link between electrophysiological modifications of dopaminergic neurons in the intermediate Ventral Tegmental Area (VTA) of RCF animals and behavioral resilience. We found reduced hyperpolarization-activated (I_h) cation current amplitude and evoked firing in VTA dopaminergic neurons from both young and adult RCF female mice. In vivo, VTA-specific pharmacological manipulation of the I_h current reverted the pro-resilient phenotype in adult early-stressed mice or mimicked behavioral resilience in adult control animals.
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Scrap and Build for Functional Neural Circuits: Spatiotemporal Regulation of Dendrite Degeneration and Regeneration in Neural Development and Disease
2021, Frontiers in Cellular Neuroscience

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Research ArticleSusceptibility and Resilience to PTSD-Like Symptoms in Mice Are Associated with Opposite Dendritic Changes in the Prelimbic and Infralimbic Cortices Following Trauma

Highlights

Abstract

Section snippets

INTRODUCTION

Animals

Labeling of mice as stress-susceptible or stress-resilient

DISCUSSION

Authors' contributions

Funding

Notes

Declaration of competing interest

Neurobiol Learn Mem.

Brain Stimul.

Eur Neuropsychopharmacol.

Biol Psychiatry.

Neuropharmacology.

Neurosci Biobehav Rev.

Addict Behav.

Neuron.

Evidence for a role of corticosterone. Horm Behav.

Biol Psychiatry.

Brain Res.

Eur Neuropsychopharmacol.

Brain Res.

Behav Brain Res.

Eur Neuropsychopharmacol.

Brain Res.

Neuroscience.

Neurobiol Stress.

J BehavTherExp Psychiatry.

Neuroscience.

Brain Res.

J Psychiatr Res.

Biol Psychiatry.

Front Psychiatry.

Behav Brain Res.

Neuron.

Effects of paroxetine on PTSD-like symptoms in mice

Psychopharmacology (Berl).

Fear extinction requires infralimbic cortex projections to the basolateral amygdala

Transl Psychiatry.

Research Article
Susceptibility and Resilience to PTSD-Like Symptoms in Mice Are Associated with Opposite Dendritic Changes in the Prelimbic and Infralimbic Cortices Following Trauma