Week 2

I was glad I read the Chaudhury et al. paper first because it made me aware of the differences between phasic and tonic firing and why both authors used phasic activation for their experiments. And though I know format should not affect my opinion of content, the fact that the articles were in the same format assisted in my ability to compare them. At first glance, I thought Tye et al. was clearer, but later I realized both experiments were well done and could convince me of their findings.

One thing I liked from Chaudhury et al. was how they looked at the VTA neurons that projected to both the NAc and the mPFC. It was interesting how the activation vs. the inhibition of these neurons resulted in different behavioral outcomes. These particular results are significant in my opinion, because in such a complex disorder, it is important to understand every part of the involved circuits in order to study depression and how antidepressants work. I was also interested in their use of the subthreshold social defeat paradigm because I was unfamiliar with it. Though I read through the methods to try to get a better grasp on the paradigm, I was still a little confused on how they quantified subthreshold defeat, for it seemed like a relative term to me that would be different depending on the mouse.

For the Tye et al. paper, I appreciated how thorough they were in their holistic approach. They tested the symptoms of depression (anhedonia and lack of motivation) along with utilizing a CMS paradigm. Since depression is such a complex disease, to be able to truly study it, you need a realistic model and I think Tye et al. has achieved the most realistic one that we have seen so far. And though they found reduced firing in the mice depression models while Chaudhury et al. found a higher firing rate, they explained how the two different methods to model depression may have resulted in opposite results. For CMS could reduce dopamine firing over the long period of time, but the more severe stressors over a short period of time from the social defeat paradigm could increase firing.

In all, I like that both papers, especially Tye et al., acknowledged how complex the circuitry in depression is, rather than attempting to make big generalizations from one set of data like the week one papers.