Tye et al. & Chaudhury et al.

In the beginning of the paper by Chaudhury et al., they speak of tyrosine hydroxylase to label DA neurons specifically, but tyrosine hydroxylase is the precursor in a chain of reactions that also leads to the synthesis of norepinephrine and epinephrine. It may be my inexperience, but it strikes me that adrenergic neurons would be labeled as well, which could throw off the entire experiment. Also, I thought that a control resilient group would be necessary for the experiment in which they investigated the effects of halorhodopsin in the NAc pathway. Without one, they are comparing two susceptible groups, and though they found significant conclusions, they would have been more compelling if compared to a resilient animal than to a susceptible animal controlled for YFP. Something else that caught my eye was that inhibition of the mPFC pathway resulted in depression-like symptoms only in the social interaction test. It might be possible that the fact that the optogenetic stimulation was during this test caused these results. My final and largest criticism is that they claim to have found evidence that shows mice that are stressed then optically stimulated during the social interaction paradigm have lasting changes in excitability, but didn’t do much of a longitudinal study. The longest period they waited was 12 hours. I think it would be much more effective to wait longer and test again, maybe making a plot of the changes in excitability seen. In the Tye et al. paper, the test to ensure that inhibition of the VTA DA neurons resulted depression-like behaviors was very well designed. They controlled for the possibility of the effect of this stimulation on muscle activity by comparing inhibition of the neurons in the same mice in an open field test. I thought that was a very comprehensive piece of the study and well done to prove causation. I also believe the graph going with this information was fantastic. However, were the data points for the sucrose preference test compared only between groups, or also within? I think a comparison of points within groups would be enlightening as it looks as though the sucrose preference of the NpHR group did not go up that much during the second period of absence of stimulation. Also, when looking at the interaction between activation of these neurons and CMS caused depression-like symptoms, the value of struggling did not return to previous levels in CMS+ChR2 animals, a finding that might be interesting to attempt to study further and explain. (The same happened with the sucrose preference test as well.) I very much liked that to test their theory on the relation of glutamate and dopamine in the TST they used antagonists to show more causation.