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Week 5: Allsop et al. and Sial et al.

The paper by Sial and colleagues outlines the Vicarious Social Defeat Stress (VSDS) paradigm, in which a male mouse observes the chronic social defeat (modification to the CSDS paradigm) of another mouse by a large retired breeder. The paper demonstrates the utility of this model in showing that emotional stress is sufficient to induce behavioral and hormonal abnormalities in the way that emotional stress (witnessing a traumatic event) has led to symptoms of depressive- and anxiety-like behaviors and even post-traumatic stress disorder in humans.

The study by Allsop and colleagues used a similar paradigm in which one mouse observed another mouse receiving foot shocks in another container after first being exposed to the shock floor of that container themselves (or not). The purpose of this study was to delineate the purpose and directionality of ACC/BLA projections in observational learning, in which an observer learns cues to avoid dangerous scenarios by watching others be physically distressed. The study found that, in acquisition of observational fear conditioning, ACC projections to the BLA is necessary, but not for expressing observational conditioning, or for learning/expressing classical fear conditioning. When this circuit was inhibited optogenetically during observation, the cue did not elicit consistent freezing during the test scenario (however, inhibition during the test had no effect).

The major difference between Allsop et al.'s paradigm and the VSDS paradigm used by Sial and colleagues is the type/origin of stress (social defeat vs. foot shock). As Allsop and colleagues briefly detail in their conclusions, this difference is noteworthy because social defeat by a dominant mouse is a natural and easily identifiable stressor. Foot shocks, on the other hand, generally don't occur in nature, but more importantly, a mouse cannot identify the source of pain when observing another mouse undergo a foot shock unless they have experience on a shock grid floor. Foot shocks aren't visible, and they don't have a specific scent in the way a dominant mouse has an identifiable scent and you can watch them being aggressive towards the smaller mouse.

Personally, I believe that the natural social defeat paradigm is more applicable to disorders like PTSD in humans, because when we witness someone experiencing a traumatic event, we generally can see or otherwise sense the source of the trauma - which is where trauma triggers usually come from. For example, seeing a gruesome car accident might lead to PTSD triggered by cars (or the specific makes/models involved in the crash), the scene of the accident, a song that was playing on the radio when you witnessed the crash, etc. I can't think of any situations where humans are stressed or injured traumatically by something unseeable, and I also can't think of how that would trigger anxious or depressive behaviors.

Allsop and colleagues connect their findings more so to social cognition disorders, such as ASD and social anxiety. One of the hallmarks of ASD is difficulty predicting reactions. Perhaps this symptom of ASD could be due to faulty connectivity between the ACC and BLA, leading to an inability to encode the cue-pain connection by watching another's behavioral reaction to pain. It would be interesting to evaluate this theory by seeing whether inhibition of ACC-->BLA circuitry is sufficient to block encoding of other observationally learned behaviors, like watching another mouse pushing a lever to get a fruitloop.

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