Decisions are customarily a result of the Reviewing Editor and the peer reviewers coming together and discussing their recommendations until a consensus is reached. When revisions are invited, a fact-based synthesis statement explaining their decision and outlining what is needed to prepare a revision will be listed below. The following reviewer agreed to reveal their identity: Norman Ruby.
2. Somewhat minor, but I find it easier to ground myself to graphs when the. control condition is presented on the left. I would suggest moving Duper mice to the right and WT to the left. I also suggest moving controls to the left and shifted to the right. 4. Phase delays seem to fragment rhythms in wt, but not in duper. The actograms show part of the activity reentraining immediately while the onsets lag behind. By contrast, within the same wt animal, phase advances are consolidated. It seems clear that light is directly disrupting the circadian pacemaker, or perhaps its output. I am surprised that the authors did not run a phase shifting study in DD to test this.
2. In some cases, it is suggested that WT animals may be differentially affected as Duper animals are protected from sustained internal desynchronization . In others, misalignment is discussed . I’m assuming that internal desynchronization refers to coordination of optimal phase among central and peripheral oscillators). I’m not sure if misalignment refers to the same or misalignment relative to the LD cycle.
For the reviewer’s information, we have performed further experiments to evaluate this inference. First, we have examined the time at which the preovulatory LH surge occurs in wt and duper hamsters subjected to an 8h advance. Our results document that the mutants complete re-entrainment of the LH surge within 4 days , while the wild types have not yet done so. Second, we have completed an RNA-Seq analysis of the transcriptional changes in the liver of duper vs.
In response to the reviewer’s comment, we have added the reference for Fig 1 in the methods section . We agree with the reviewer that simplification of the data in Fig. 3 would be helpful. Accordingly, we have changed the presentation of the data in Fig. 3E from bar graphs to pie charts as was done in other adult neurogenesis papers
The fragmentation of the locomotor activity in hamsters upon shifts of the LD cycle is complicated by masking, particularly during 8h phase delays. The animals show a combination of re-entrainment of the circadian system and masking: suppression of locomotor activity due to their avoidance of exposure to light. We have examined this in males by combining 8h shifts with transfer of animals to DD after the first 2 shifted cycles . This allows us to better assess the phase of the oscillator.