Dear Editor,
We would like to submit the enclosedmanuscript entitled "GDNF Acutely Modulates
Neuronal Excitability and A-type PotassiumChannels in Midbrain Dopaminergic Neurons",
which we wish to be considered forpublication in Nature Neuroscience.
GDNF has long been thought to be a potentneurotrophic factor for the survival of midbrain
dopaminergic neurons, which are degeneratedin Parkinson’s disease. In this paper, we
report an unexpected, acute effect of GDNFon A-type potassium channels, leading to a
potentiation of neuronal excitability, inthe dopaminergic neurons in culture as well as in
adult brain slices. Further, we show thatGDNF regulates the K channels through a
mechanism that involves activation of MAPkinase. Thus, this study has revealed, for the
first time, an acute modulation of ionchannels by GDNF. Our findings challenge the
classic view of GDNF as a long-termsurvival factor for midbrain dopaminergic neurons,
and suggest that the normal function ofGDNF is to regulate neuronal excitability, and
consequently dopamine release. Theseresults may also have implications in the treatment
of Parkinson’s disease.
Due to a direct competition and conflict ofinterest, we request that Drs. XXX of Harvard
Univ., and YY of Yale Univ. not beconsidered as reviewers. With thanks for your
consideration, I am
Sincerely yours,
Dear Editor,
We would like to submit the enclosedmanuscript entitled "Ca2 -binding protein frequenin
mediates GDNF-induced potentiation of Ca2 channels and transmitter release", which we wish
to be considered for publication in Neuron.
We believe that two aspects of thismanuscript will make it interesting to general readers of
Neuron. First, we report that GDNF has along-term regulatory effect on neurotransmitter
release at the neuromuscular synapses. Thisprovides the first physiological evidence for a role
of this new family of neurotrophic factorsin functional synaptic transmission. Second, we
show that the GDNF effect is mediated byenhancing the expression of the Ca2 -binding
protein frequenin. Further, GDNF andfrequenin facilitate synaptic transmission by enhancing
Ca2 channel activity, leading to anenhancement of Ca2 influx. Thus, this study has identified,
for the first time, a molecular target thatmediates the long-term, synaptic action of a
neurotrophic factor. Our findings may alsohave general implications in the cell biology of
neurotransmitter release.
Dear Editor:
Enclosed are copies of a manuscriptentitled "BDNF and NT-4/5 Promote the Development of
Long-Term Potentiation in theHippocampus", which we wish to be considered for publication in
Nature. As you know, there is a great dealof interest and excitement recently in understanding the
role of neurotrophins in synapsedevelopment and plasticity. Our manuscript provides, for the first
time, the physiological evidence thatneurotrophins regulate long-term potentiation (LTP). The
main point of the paper is that theneurotrophins BDNF and NT-4 induce an earlier appearance of
LTP in developing hippocampus. In contrastto recent Science article by Erin Schuman"s group,
we (and several other LTP groups) did notsee that BDNF enhance basal synaptic transmission in
adullt hippocampus. However, we found thatin adult hippocampus, inhibition of BDNF/TrkB
activity attenuated LTP, and weak tetanus thatnormally cannot induce LTP produced enduring
LTP. These findings may have implicationsin the basic mechanism for regulation of synapse
development and long-term modulation ofsynaptic efficacy.
Because of the rather competitive nature ofthe field and the important implication of our findings,
we have not yet presented this work in anypublic forum. However, confidential discussion with
several prominent neuroscientists such as111 and 222 have generated tremendous excitement.
Thus, we feel that this work is of generalinterest and is suitable for publication in Nature. We
would like to suggest Drs. aaa of YaleUniv., bbb of Harvard Medical School, and ccc of Univ. of
California-Berkeley, as reviewers for thismanuscript. Due to a direct competition and conflict of
interest, we request that Dr. XX and YY.not be considered as reviewers.
Thank you very much for your consideration.
When your paper gets rejected – withoutreview
Dear Editor,
I would appreciate if you could reconsiderto review our manuscript, “111." We
feel strongly that this is an importantsubject that touches one of the central dogmas in
neuroscience: xxx. It is also very timely,given the publication of the paper by X and Y
entitled “222” in the latest issue ofNature Neuroscience. In this paper, the authors
xxx. They claimed that xxx. When a paperthis provocative has been published by a
high profile journal like NatureNeuroscience, we believe that it is worth giving a
benefit of doubts. It will be helpful ifthere are papers that consider other alternative
interpretations, or attempt to replicate inthe same or different systems.
We have observed similar xxx, but we have acompletely different interpretation.
We found that 1) xxx 2) xxx; 3) xxx. Thus,our paper raises the possibility that xxx
reported by X and Y were due to xxx.Specifically, we would like you to consider the
following two issues: First, X and Y usedaaa, while we used bbb. sssssssss. Second,
ccc used by X and Y may not be so specific.
In addition to the drastically differentopinions regarding xxx, we feel that our
findings on xxx is also significant in yyyand will be of interests to general readers of
Nature Neuroscience. We therefore did notwrite our paper to directly challenge the
paper by X and Y. However, we will bewilling to re-write the paper in ways you think
that will help debate on this importantissue.
When your paper gets rejected – with review
Dear Dr. xx,
We received with some surprise your letterof November 4, rejecting this manuscript on
the basis of one reviewer’s opinion whichyou “found persuasive”. We wish to indicate our
dissatisfaction with this reviewer’scomments, which appear to ignore the new experiments
submitted as part of the revisedmanuscript.
This reviewer states: “111.” This wasprecisely the point of the xxx experiment which
indicated that there were no such deficits.
This reviewer further states: “222.” Again,this is a mystifying statement as the detailed
rebuttal accompanying this letter describedthe xxx. Did the reviewer not understand that
xxx?
Finally, concerning the proposal for a xxxexperiment, we believe that you and this
reviewer already know that xxx. Thus, it isimpossible to do such experiments.
While we recognize that the final decisionis yours, we feel that reviewer#1 is being
unreasonable. We would greatly appreciateit if you would submit this manuscript,
reviewer#1’s comments, and our rebuttals,to an additional unbiased reviewer. We would be
most surprised if the new reviewer wouldsee the comments of the reviewer#1 as reasonable,
but if he/she did so, we would accept anegative decision gracefully.
