Skip to main content

Blog 6: Ayhan et al (2011) and Burrows et al (2015)

By
Ayhan et al (2011) and Burrows et al (2015) examine different aspects of behavioral phenotypes typically seen in schizophrenia using transgenic and knockout mice models. Ayhan et al was an interesting read in terms of the gender-specific (and sometimes gender-non-specific) effects that were found throughout the experiment. For example, the noted effects of hDISC1 on immobility in the FST and TST were only significant in females while the effects of MK-801 and amphetamine (i.e. greater total locomotor activity) were only significant in males. I would have liked to see a comprehensive comparison and delineation of this gender-based data much like Table 1 to round out the article. This could be especially helpful for future experiments that examine the specifics of the temporal onset of schizophrenia, since it is widely known that human females generally display symptoms roughly 3-5 years later than males. To the authors’ credit, they acknowledge in the discussion that further experiments are certainly needed to look at gender differences in more detail, despite the data appearing to show gender associations between DISC1 and cognitive functions and disease frequency. 

For Burrows et al (2015), the primary question I had from their setup was the significance of using prepulse inhibition (PPI) and showing that environmental enrichment ameliorated the effects of it in the mGlu5 knockout group. My best attempt at understanding was that PPI involves delivering a ‘quieter’ stimulus before a startle pulse and the authors expected to induce an increased startle response in the animals injected with MK-801 compared to saline. However, how does the setup of the pulse trials and especially the variable intervals at which they were delivered fit into its function and purpose? The discussion briefly mentions how this finding could draw a parallel between the therapeutic effects of an enriched environment and pharmacological treatment. I can see where this comparison comes from in the data of Figure 5a, but I am still not fully grasping how PPI itself could be translated to a clinical model. Although a more comprehensive understanding of that protocol would give me a greater sense of confidence in this treatment recommendation, I still appreciate how the paper highlights a mix of genetic and environmental effects on schizophrenia to ensure that both are recognized as contributors to the development of this complex disorder. 

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