Biopsych seminar 2020

March 9 Papers: Ayhan et. al, Burrows et. al The Disrupted In Schizophrenia 1 (DISC1) gene plays a role in both brain development and in adult brain function by helping carry out activities such as neurogenesis, neuronal migration, and dendrite maturation. However, past research has shown that mutations in this gene are a significant risk factor for the development of schizophrenia and some mood disorders. Ayhan et al’s 2011 study examined the varying neurobehavioral effects that the mutant protein hDISC1 has on mice at different stages in development. They investigated the roles hDISC1 played when expressed only during prenatal development, only during a postnatal period, or when expressed both pre- and postnatally. Their results found that the effects of hDISC1 vary widely depending on when in neurodevelopment the protein is expressed, with the most significant effects being observed when the mutant is expressed both prenatally and postnatally.  I found this paper to be v...

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 depressi...

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...

The first article by Sial et al, published in 2015, explores the effect in terms of depressive behaviors of forcing mice to witness a traumatic event (the abuse of another mouse by an aggressor) with a paradigm called the vicarious social defeat stress model (VSDS). After understanding this experimental set up, one thing that out to me right off the bat was how this model may or may not accurately represent PTSD as it aims to do. First of all, although witnessing a traumatic event may cause PTSD, we know that it is not guaranteed to do so. In humans I am aware that there are other factors that go into developing PTSD besides just the traumatic event itself - resulting in varying PSTD responses from person to person. Although the experiment results support the fact that witnessing a traumatic event may induce emotional stress and depressive like phenotype in mice that are similar to if the mouse were experiencing the physical pain, itself, I am left wondering if other factors played in...

The first of the two papers, Sial et al. was a very easy-read. I love a straight-forward methods paper and thought the concept was interesting approach to modeling PTSD. It would have been nice to see measures of anxiety other than just the elevated plus maze and social interaction task. Something else that they also mention very briefly at the beginning of the paper is the fact that the social hierarchy of the mice that are kept together might have affected the results. This made me think that maybe if the observer mouse had been watching a strange mouse get attacked rather than one of its littermate’s the results would have been significantly different, similar to how if I saw a stranger get beat up vs. my sibling I might respond differently. A limitation Sial et al. mentioned was how they had been unsuccessful getting their experiments to work in females due to attacker mouse being more interested in a female observer rather than attacking the other male. This made...

Vicarious stress, which Sial et al and Allsop et al studied in their experiments, is an important component of understanding psychological disorders. Since the beginning of psychology as a field, psychologists have published many different theories of emotion and learning and the mechanisms that underlie their behavioral responses. However, recreating these theories to ethically test their validity in rodents has been, and still is, a challenge. Through their observational learning tasks, Sial and Allsop show ways in which learning vicariously can elucidate the biology that underlie PTSD-like phenotypes. Sial et al propose a novel vicarious social stress paradigm in which mice can experience emotional stress rather than physical stress, as other forms of social defeat stress include. This model of emotional stress does a nice job of showing that emotional stress, although it may not be immediately apparent, has similar effects on a rodent’s corticosterone levels and...