Skip to main content

Post 2:Dopamine circuits and recovery from stress

By
            The two papers this week were published in the same year, in the same journal, and on the same topic. They both looked at dopamine’s role in depressive-like behaviors. Both groups utilized optogenetics and phasic firing in the ventral tegmental area. With all of the similarities, it was shocking that both research groups came to completely different conclusions. After reading the papers, I went back to re-read them to establish the differences that could account for the opposite conclusion. The main methodology difference that I found was in the stress protocol. Chaudhury used a social-defeat stress model and Tye used a chronic mild stress paradigm. According to the articles, both are established models for inducing depressive-like behaviors. So, why did phasic firing in the first experiment lead to resilient mice becoming susceptible while in the latter experiment, it led to the rapid rescue of this depressive phenotype?
            My best guess would be that the social-defeat stress model established more of an acute depressive state, whereas the chronic mild stress parallels chronic depression. This thought was validated when I read the article in Discover. The author creates an analogy with getting mugged and being consistently worried about job security. The different experiences could alter the brain in a different way, even though they both may act within the same circuitry. Relating this back to our discussion last week, depression presents itself in many forms. We talked about how anxiety closely relates to depression and how anxious behavior is often indicative of depression. But depression does not always manifest itself in anxious behavior – some people can’t get out of bed, are lethargic, and have no interest in things. Perhaps the differing results then confirm what we already know: depression affects everyone differently. This then raises a lot of questions. If depression affects people so differently based on their experiences, what is the best way to go about studying it and ultimately treating it? If there was such a quick reversal of effects in these studies, is there a way for us to see a quick reversal of depression in humans without waiting for SSRIs to kick in?

Comments

Post a Comment

Popular posts from this blog

Week 2- Dopamine Modulation of Depressive-like Behaviors

By
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...
Post a Comment
Read more

Sial & Allsop

By
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...
Post a Comment
Read more

Buffington and Reber

By
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...
Post a Comment
Read more