Hello Dr. Vadovičová,

I'd be happy to review the article, but at first glance, it appears that it will need a great deal of editing, including the abstract, which starts awkwardly with "My findings show, for the first time ...." Would you mind if I make the edition and send it back to you to see what you think?

Thank you,

Ramsis Benjamin, MD, MPH

Dear Dr. Ramsis Benjamin,

I would be glad for your review and comments.

First sentence means that paper shows first ever circuit-based neural causes for loss of awareness, anesthesia, slow-wave sleep, OIRD.. I read in a Chinese review paper that causes of anesthesia are unknown yet. Thus I was asked to state what are my findings and cite what are others findings.

Understood. Give me a few days to go over your article in detail. I'll send version 10 probably by next weekend.

Take good care.

Hello Dr. Vadovičová,

I've edited your article and made a few recommendations. The title is modified to fit the body of the article. Some sections were deleted as I found them not pertinent to your main idea.

Hope this helps. Once you make the necessary corrections and approve the final draft, I can provide a peer review. Best of luck,

Ramsis Benjamin, MD, MPH

Dear Prof. Ramsis Benjamin.

Thank you for your reply.

Why would you delete 'anesthesia' from the title? and why you changed the neural connectivity data for few brain regions in the Abstract? there are many references for the anatomical connectivity.

From what I gather, the crux of your argument is the effects of opioid-induced respiratory depression on the Medial Habenula. Ketamine is not an opioid. I think your manuscript is too broad and too wordy. It would help if you inserted some fMRI.

You may wish to divide your manuscript into two distinct articles: one for opioids and the other for anesthesia. There were many duplicate pathways that may need to be abridged. As it is, the article is too hard to digest and understand.

Of note, the abstract should be free from any references and no more than 500 words.

Hopefully, this helps.

RB

No. My paper shows how activation of the medial habenula-IPN projections causes anesthesia, loss of awareness, SWS, and memory replay.

My work claims for the first time that mu-opioids ACTIVATE the MHb, while ketamine, 5-HT2a, and phencyclidine activate the IPN.

I proposed that many other anesthetics activate the MHb-IPN or IPN output, and that gabaergic IPN projections inhibit the vPAG. vPAG is known to induce arousal and activate many arousal promoting brain regions.

I want to show what is the role of the MHb-IPN-MRN pathway, as well as the MHb-IPN-hippocampus, MHb-IPN-BF, MHb-IPN-PAG, and IPN-MRN-claustrum-cortical SWA pathway. As these roles were unknown before, thus it is useful to inform about them in title and paper's abstract.

Karin

Hello,

Thanks for your response. Now I understand what you are trying to do. Perhaps you can simplify your paper into two main sections: 1) Activation of MHb-IPN causes anesthesia (Figures would help to illustrate this), and 2) Activation of MHb by mu-opioids separate from activation of IPN by ketamine, 5HT2a and PCP also causes anesthesia and SWS (Figures again would help)?

I think if you keep the two ideas separate and make it more concise, your conclusion would be more concrete in combining the two pathways to produce the same effect, and you'd be able to publish the paper. These are just my opinions.

Best of luck.

RB

Hello,

Thank you for your advice and opinion.

Kind regards,

Karin