This is, in summary, an interesting study aimed to review the role of the lateral septum (LS) in anxiety, depression, eating disorders and their comorbidity. The author reported that LS represents a common site for the comorbidity of neuropsychiatric disorders, and therefore a potential pharmacological target. Importantly, LS is both anxiolytic and anxiogenic and it can promote and inhibit feeding.

The author may find as follows my main comments/suggestions.
First, as the authors, throughout the Introduction section, correctly reported that the medial septum (MS) is cellularly heterogeneous consisting mostly of excitatory glutamatergic and modulatory cholinergic neurones and that LS receives glutamatergic input predominantly from the ventral hippocampus, the properties and impact of glutamatergic drugs targeting NMDA receptors located in MS with an antidepressant activity could be briefly mentioned. Importantly, glutamatergic system in MS represents a target for effective intervention in major depression and glutamatergic medications targeting NMDA receptors by inhibiting the release of neurotransmitters or modulating its post-synaptic responses may serve as molecule modulators with specific antidepressant properties. Thus, given the importance of this topic, i suggest to cite within the main text the article published on Curr Pharm Des (PMID: 23173582).

In addition, at the molecular level, specific microRNAs may contribute to the neuroanatomy of the septum with miRNA dys-regulation which is linked to several neuropsychiatric diseases and their treatment. Thus, given the possible contribution of microRNAs in elucidating the mechanisms of the septum (although i understand that the link between microRNAs, the septum and psychiatric conditions is not the main topic of the present paper), i suggest to cite throughout the main text the article published on Neurosci Res about this theme (PMID: 22521503).

This is particularly relevant as the same authors, more ahead, referred to the importance of established treatments for depression, such as selective serotonin reuptake inhibitors.

Moreover, as the most relevant aims/objectives of the present review have been provided, the most relevant hypotheses underlying this study might be described in a more detailed manner.

Also, the assumption that LS plays a role in anxiety/depression based on early lesioning studies could be reported in a more detailed manner. Here, i suggest to insert a table in the effort to summarize the most relevant information/details and existing studies related to the role of LS in anxiety/depression.

In addition, some statements such as “LS outputs are anxiolytic and anti-depressive” or “current evidence suggest a bidirectional control of anxiety by the LS, and a physiological role in feeding. However” are interesting as presented but could be further developed.

Importantly, the main limitations/shortcomings might be provided more extensively.

Finally, what is the take-home message of this manuscript? While the authors reported that chemogenetic and optogenetic techniques identified several novel circuits involving the LS that regulate anxiety and feeding, they failed, in my opinion, to focus on some conclusive remarks to this specific regard. Specifically, what are the main implications of this paper? Here, some additional details might be useful for the general readership.

In the revised manuscript, the authors addressed most of the major questions raised by Reviewers improving both the main structure and quality of the present paper. I have no further additional comments.