Skip to main content

Week 5: PTSD and observational conditioning

The Sial et al. paper was published in 2015 and took an emerging approach to modeling PTSD in male mice by delineating between physical and emotional stress. Of the previous papers we have discussed, many of them implemented stress paradigms including chronic mild stress (CMS) and social defeat stress, where the animal is personally experiencing the stressor or trauma. The Sial paper used a vicarious social defeat stress (VSDS) paradigm, in which a mouse witnesses another mouse undergo social defeat stress (SDS). By being a third party witness, the lab was able to induce PTSD-like symptoms through emotional stress, rather than physical stress. 
            After several weeks of alluding to the topic of PTSD during discussion, I was excited to dive into this topic at a more direct approach. We previously discussed how the social defeat stress paradigm seemed more analogous to a PTSD model rather than anxiety or depression as (CMS) might. Taking this approach one step further to study the effects of witnessing these traumatic events I was immediately intrigued by the use of the VSDS model. It was not surprising to me that VSDS exposure resulted in phenotypic behavior associated with PTSD including the social avoidance. I was more impressed with the data showing increased cortisol levels and the reversibility of behaviors with fluoxetine. The changes in cortisol levels was a physical response to an emotional stressor, which in my eyes shows how much consistency there is with physiology and psychopathology, an overlap I fell is misunderstood by the general public resulting in the continued stigmatization of mental illness. I was intrigued by the effectiveness of fluoxetine as a treatment option for stress induced behaviors because of the application to clinical practice, a topic we have struggled to connect to previous papers in our discussions. With clinical advancements being a top motivation for animal research, it was refreshing to read about a translational treatment option. 
            The Allsop et al. paper was published in 2018 and piggy backs off of several concepts stemming from the Sial paper which were not thoroughly addressed. The Allsop paper studies the neuronal patterns necessary for observational learning in the context of aversive social stimuli, or fear conditioning. This paper takes an in-depth look at the connection between the anterior cingulate cortex (ACC) and the basolateral amygdala (BLA) and its involvement in observational fear conditioning. With the knowledge from the previous paper that witnessing traumatic events is sufficient to induce emotional and physiological responses it was no surprise the amygdala was involved as well as the ACC which is largely implicated in emotion as well as social processing. Along with providing a picture of the neural circuits involved in the behavioral patterns observed in the first paper, the Allsop article also demonstrates how stress can physically change these circuits, which is consistent with the idea the PTSD has several neurophysiological effects in humans. With the combined knowledge from these two papers, I believe a more complete picture is painted of the models which may induct PTSD-like behaviors, the behavioral effects of these stress paradigms, the circuitry involved, and possible therapeutic interventions. Alone, neither of these articles felt complete, however after having read both I am curious to read more about the effects of witnessing trauma, previous life experiences and accumulative trauma, and potential interventions to treat the physical and emotional symptoms seen clinically in PTSD patients. 

Comments

Popular posts from this blog

Week 2- Dopamine Modulation of Depressive-like Behaviors

The Chaudhury et al paper explored the neural circuit mechanisms involved in the dopamine modulation of certain symptoms of depression. In this study, the researchers looked at social interaction and sucrose preference as part of their social-defeat paradigm, which has been shown in the past to be indicative of depressive-like behaviors. Although I initially did not completely see the connection between the social-defeat stress model of depression and the tonic vs phasic firing of dopamine neurons, it seemed that susceptibility and resilience to stress played a role in the functional/behavioral effects of dopamine firing. It was interesting to see how chronic mild stress with phasic firing of VTA dopamine neurons converted even resilient mice into susceptible mice.  The Tye et al paper similarly looked at the dopamine modulation of depressive-like behaviors, focusing on motivation with the forced swim tests and open field tests, followed by measurement of anhedonia by quantifyi...

Sial & Allsop

Sial et al. derived a novel approach for studying what they deem vicarious defeat stress (VSDS) as a model for MDD, PTSD, and other mood-related disorders as an alternative to the classical CSDS paradigm. Using adult male mice, they demonstrate that their model induces a robust and measurable social avoidant phenotype as well as other stress and anxiety related behavioral outputs. Their subsequent rescue study with chronic fluoxetine treatment shows reversal of the behavioral phenotypes and emphasizes the predictive validity of the model. Allsop et al. found that BLA-projecting ACC neurons preferentially encode socially derived aversive cue information by encoding the demonstrator’s distress response during observational learning, hence enabling acquisition of negative valence of cue by BLA neurons and behavioral output. In order to test their hypothesis, Allsop et al. used an observational fear conditional paradigm to create association between a conditioned stimulu...

Buffington and Reber

Buffington et al. explore a mechanism by which maternal obesity can induce neuronal and subsequent behavioral disorders. Using a model of high-fat diet (MHFD)-induced obesity, the authors showcase the strong connection between the brain and the gut, and its impact on behavior. The findings are provocative; by exposing these offspring to the microbiome of control offspring, there was evidence of a rescued observed behavioral phenotype. Furthermore, a phylogenetic profiling of the gut microbiome revealed a decrease in L. reuteri within MHFD offspring, and introduction of live L. reuteri into the drinking water shows successful rescue of the behavioral issues in the MHFD offspring. L. reuteri-induced expression of oxytocin within the paraventricular nuclei of the hypothalamus provides a potential mechanistic explanation for the behavioral changes. I thought this paper provided robust support for the hypothesized interaction between the gut biome and the developing CNS, with tremendous po...