Reviewer #2 (Public Review):

In this paper, Boi et al. thoroughly classified the electrophysiological and morphological characteristics of serotonergic and dopaminergic neurons in the DRN and examined the alterations of these neurons in the 6-OHDA-induced mouse PD model. Using whole-cell patch clamp recording, they found that 5-HT and dopamine (DA) neurons in the DRN are electrophysiologically well-distinguished from each other. In addition, they characterized distinct morphological features of 5-HT and DA neurons in the DRN. Notably, these specific features of 5-HT and DA neurons in the DRN exhibited different changes in the 6-OHDA-induced PD model. Then the authors utilized desipramine (DMI) to separate the effects of nigrostriatal DA depletion and noradrenalin (NA) depletion which are induced by 6-OHDA. Interestingly, protection from NA depletion by DMI pretreatment reversed the changes in 5-HT neurons, while having a minor impact on the changes in DA neurons in the DRN. These data indicate that the role of NA lesion in the altered properties of DRN 5-HT neurons by 6-OHDA is more critical than the one of DA lesion.

Overall, this study provides foundational data on the 5-HT and DA neurons in the DRN and their potential involvement in PD symptoms. Given the defects of the DRN in PD, this paper may offer insights into the cellular mechanisms that may underlie non-motor symptoms associated with PD. Despite the importance of the primary claim proposed by the authors, however, several weaknesses undermine the significance of the data.