This study by Higgins et al describes the temporal and spatial expression of lepRb in the developing post-natal mouse hypothalamus. Previous studies have shown lepRb in some hypothalamic nuclei (particularly the ARC), but many of these have been using techniques that have now been superceded by more accurate techniques. This study uses RNAscope that allows for spatial analysis, examines the receptor in both sexes, and investigates a wider range of time points and nuclei (less explored but nonetheless important regions such as the PVH, DMH and LHA). The authors have reported the temporal pattern across 5 target hypothalamic nuclei (ARC, VMH, DMH, PVH, LHA) and reported age dependent changes in all regions except the LHA, consistent with a role for leptin signalling in the target destination of ARC neurites, as well as in the ARC LepRb expressing neurons themselves. The authors also find interesting sex differences in expression of LepRb in the VMH, which is interesting given the many sex- specific behaviours controlled by the VMH (glucose sensing, sexual behaviours, agressive behaviours). The text is very well written and clear, and the figures are easy to interpret.

I have a few minor points and questions that I feel could enhance the manuscript:
1) The authors imply in the first paragraph of the introduction that ARC POMC and NPY/AgRP expressing neurons project to the VMH, but it was my understanding that these neurons do not project here (PMID: 30661757).
2) The authors have displayed nicely in Fig S3 the comparison between their plasma leptin levels in the post-natal period and previous studies. Can they comment on why the magnitude of the leptin surge is lower in the current study than previous studies?
3) Within groups (male/ female at each age) there is a variation in both plasma leptin levels and LepRb mRNA levels. Is this variation explained by litter (i.e. are animals that are high/ low at each timepoint litter mates?) Also, if the plasma leptin measurements and lepRb mRNA expression were measured in the same aninals, is there any correlation between the two?
4) In the experiments attempting to define which population of PVH neurons express the LeprB, the authors have shown the % of PVH LepRb cells that express the marker of interest. However, I wonder if it might also be interesting to show this expressed the other way. For example, the authros show that 25% of LepRb cells in the PVH co-express MC4R. But if the authors are hypothesising that leptin signalling in MC4R expressing neurons in the PVH is responsible for the attraction of ARC neurites to these targets, it would be interesting to know what % of MC4R expressing cells co-express LepRb.

The authors have answered my questions sufficiently with justification of why they cannot provide data to clarify some issues.