I really enjoyed this article. It should certainly spur a number of studies into the targets of CREB, the mechanisms of the increased expression of CREB as a result of stress, as well as similar studies on other transcription factors which may play a role in stress.

The brain region I thought might have been most affected by stress, the hypothalamus, was included in the analysis and showed some responsiveness. I was surprised the authors did not show any data regarding the amygdala. It is clear that stressors result in gene expression changes in certain subnuclei of this region.

One other critique is that the methods for analysis should be amenable to quantification of the expression changes at the levels of specific subnuclei of interest (for instance the raphe were mentioned as one region which might be served well by further specifying the regions showing upregulation). I believe by looking at the subregions of the hypothalamus one might see changes that are much bigger than that resulting from analysing the hypothalamus as a whole. The PVN, with its local concentration of CRF peptide containing neurons, might be expected to show much higher stress responsive changes compared to the hypothalamus as a whole. Moreover, if one looks at the amygdala, certain subnuclei might prove to be of particular interest. Given the amount of work involved in generating the animals and performing the study, it might be worthshile to maximize the impact of the data by subdividing the regions as much as possible.

But again, I thought this study to be very valuable, involving a lot of work, with the potential to spur a number of different types of studies.