Tye and Chaudhury - Week 2

While I’m not entirely sure of the reason, I find myself having a stronger preference for Tye et al.’s paper and experiments. It may partially be due to the fact that from the start I find their animal model for depression to be stronger, comparing their twice daily CMS events for 8 – 12 weeks with Chaudhury et al.’s subthreshold social-defeat paradigm for only 10 days. Given that a clinical diagnosis of depression requires 6 or more months of depressive symptoms the longer-term CMS paradigm seems a more valid set-up for a mouse model of depression. On the same note of comparing paradigms one component that, though minor, I can’t seem to shake about Chaudhury et al.’s paper is that there is no elaboration on what a “subthreshold” social defeat paradigm is. I took it upon myself to look through the supplementary information, the methods and do a Google search because for some reason I kept wondering what importance the “subthreshold” aspect of the paradigm might have. From scanning various articles online I’ve come to determine that when subjected to this paradigm style animals experience a “subthreshold” level of stress, which I assume is comparative to a baseline of some sort perhaps? Unfortunately, I’m at a mental roadblock when it comes to the paradigm, which at only 10 days with some ambiguous “subthreshold” level of stress or social defeat doesn’t seem like it is the most efficient model that the authors could have implemented.

Beyond the paradigm structure there were a few other favorable aspects of the Tye et al. paper in my opinion. While I realize that most studies require controls to eliminate simpler or alternative explanations of results, I found the inclusion of the OPT to observe any differences in locomotion was important. Locomotion can be a factor influenced by depressive-like behaviors or states so one would think there might be a decrease with the VTA inhibition. Though the control did serve its purpose of ruling out any gross motor changes, I found it interesting that there weren’t any significant differences even with the decrease upon inhibition. In the same experiment but with VTA activation I was surprised to see that both the CMS and non-CMS control groups displayed similar, and lower, velocities in Fig 2d. According to the statistics there was no significant difference yet again, but I personally would have expected the non-CMS control to have higher velocities, at least for a longer time than just the start of the experiment. In my experience working with mice when they are placed into a novel setting they spend a good amount of time exploring the area, so I definitely would have thought the non-CMS mice would behave similarly.

I also found the discussions and experiments on the neuronal properties very interesting, though to be honest I don’t feel that I fully understand what it all means so I’ll stick to what I’m more comfortable with for this discussion.