Skip to main content

Gut-Brain Axis

The papers for this week aimed to investigate the role of the gut-brain axis in stress and neurodevelopmental disorders. While we know that our microbiome influences brain function and certainly has some down-stream effects on behavior, the exact mechanisms by which this happens are complex and still not fully understood. 

Reber et al. demonstrated that immunization with an immunoregulatory environmental microorganism (M. vaccae) can rescue a stress phenotype induced with subordinate colony housing. I found the data in this paper very compelling, and the data clearly shows that immunized mice exhibit many more “proactive” behaviors than non-immunized mice, but I did wonder if there was a way to get a more complete picture of dominance status. Here, they compared the number of proactive behaviors (attacks, chasing) to reactive behaviors (flight, avoiding), to determine the dominance score of every animal. However, they only did this with male mice with other male aggressors, and I felt that their definition of proactive behaviors was incomplete. For instance, could they have monitored the vocalizations of the mice, or perhaps motion tracking? Also, what would the data look like if the aggressor was a lactating female? 

The second paper, by Buffington et al., examined the correlation between maternal obesity and neurodevelopmental disorders in offspring, particularly with respect to autism. Most interestingly, pairing MHFD (maternal high-fat diet) mice with MRD (maternal regular diet) mice restores the microbiome of the MHFD mice, and ultimately improves their social behavior. They also repeated a similar experiment by re-introducing L. reuteri into the microbial landscape of MHFD mice, which promotes oxytocin levels and therefore plays an important role in social behaviors. What I found interesting is that re-introducing L. reuteri had no effect on repetitive behaviors or anxiety of the mice (as exemplified in the marble burying paradigm), and only altered the social behavior of the mice. Does this in fact suggest that repetitive behaviors are not dependent on the microbiome? I certainly would have expected anxious behaviors to be influenced by the microbiome, so I would have liked to see a more detailed analysis of this

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...