On 2015 Dec 28, Marco Weiergräber commented:

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On 2015 Dec 07, Marco Weiergräber commented:

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On 2015 Nov 10, Marco Weiergräber commented:

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On 2015 Nov 10, Toni Schneider commented:

The comment of Marco Weiergräber is full of speculation. But scientific progress depends on careful control of novel hypotheses, especially when results of a similar research project are opposite. Scientific reports must mention opposite results, when new data are published. Siwek et al (Sleep 2014 May 1;37(5):881-92) did not refer to our results published a year earlier (Somnologie, September 2013, Volume 17, Issue 3, pp 185-192) but they speculate since then in an unscientific manner about our data, which were presented in our publication in an absolute transparent way (single data, in parallel to the resulting mean values). Our data are as reliable as the data from Siwek et al (2014). Taking this premise serious, one has to think about reasons for differences of results in an objective way. Two different mouse models were used in the two sleep studies mentioned. Logically, one must look for differences in these two mouse models, which we have discussed in an objective and fair way, without questioning the careful investigation done by Siwek et al (2014). To think about the different remnants left in the two different Cav2.3-knockout mouse lines should generate new hypotheses instead of condemning the results of a competing laboratory. We estimate the risk of an aminoterminal Cav2.3-peptide (resulting from the expression of exon 1) lower to contribute to calcium current disturbances as the risk of a "hemichannel".

The last chapter of Marco Weiergräber's comments also stays speculative, as long as he has not tested the transfer capacity of the transmitter device under discussion (a F20EET radiotransmitter from DSI). We tested the frequency bands under standardized conditions and can confirm that the bandwidth is broader than mentioned by him. Instead of repeating again and again the same critisism without mentioning e.g. a correction published by us (Schneider T. and Dibué M., 2015 in Somnologie 17, 307-308) and without presenting new proofing data, it seems to be a fight for something else but not for progress in Science.

On 2015 Oct 30, Marco Weiergräber commented:

This review article is dealing in major parts with a comparison of the work of Münch et al., "Cav2.3 E-/R-type voltage-gated calcium channels modulate sleep in mice" (Somnologie, September 2013, Volume 17, Issue 3, pp 185-192) and Siwek et al. "The Cav2.3 R-type voltage-gated Ca2+ channel in mouse sleep architecture" (Sleep. 2014 May 1;37(5):881-92. doi: 10.5665/sleep.3652). Following the publication of Münch et al. (2013), our group has raised substantial criticism to their work. For detailed information see: Weiergräber: "How do Cav2.3 voltage-gated Ca2+ channels affect sleep architecture?" (Somnologie, December 2013, Volume 17, Issue 4, pp 304-306) and Weiergräber: "Cav2.3 R-type Ca2+ channels in mouse sleep architecture—an update." (March 2015, Volume 19, Issue 1, pp 61-62) and Weiergräber: "A scientific assessment of Cav2.3 voltage-gated Ca2+ channels in rodent sleep architecture." (Sleep. 2015 Mar 1;38(3):501-2. doi: 10.5665/sleep.4520).

We had identified major experimental and analytical drawbacks in the study of Münch et al. (2013) that require -to our opinion- a total reperformance of the small sleep study performed by Münch et al. (2013). The numerous fundamental deficiencies in Münch et al. (2013) are not listet here again. We strongly advice reading our aformentioned commentaries.

However, instead of reperforming their study, Schneider and Dibue replied that the different mouse models might account for the differences in sleep study results between the groups (Schneider and Dibue, Somnologie, December 2013, Volume 17, Issue 4, pp 307-308 and Schneider and Dibue, Sleep. 2015 Mar 1;38(3):499. doi: 10.5665/sleep.4518). Although scientific reality tells a different story, Schneider and Dibue continue to suggest that the Schneider model of Cav2.3-/- might be superior to the Miller model of Cav2.3-/- which we used. In our response (Weiergräber: "A scientific assessment of Cav2.3 voltage-gated Ca2+ channels in rodent sleep architecture." Sleep. 2015 Mar 1;38(3):501-2. doi: 10.5665/sleep.4520) we have clearly elaborated that this explanation which is again repeated here in this review does not hold true and has no scientific basis. The suggestion that Cav2.3 fragments in the Miller model could form functional channels is not only speculative, indeed, publications by Annette Dolphins group (e.g. Raghib et al., 2001) has shown that it simply does not occur. Although we have communicated this fact to the authors repetitively, they again ignore it and they also did not cite our commentaries which might have helped to avoid their misleading argumentation again.

In order to comment or review their data it's mandatory for Münch et al. (2013) to first reperform their experiments to acquire valid sleep data, second to analyze for compensatory mechanisms in their model (which we did in the Miller model, but they did not in their model, at least they did not report) and finally, the Schneider model has to be evaluated for potential N-terminal peptide fragments and their influence on Ca2+ channel physiology. Finally, the authors cite Dibue et al. (2014, Epilepsia). We have explained to the authors in detail (Weiergräber and Papazoglou, Epilepsia. 2015 Jul;56(7):1180-1. doi: 10.1111/epi.13041.) that the gamma data presented there are not valid as the analysis of gamma up to 500Hz is not possible with the transmitter type they used (a F20EET from DSI with 1-50Hz bandwidth and 250 Hz nominal sampling rate). The Nyquist-Shannon-limit does not allow for analysis of such high gamma as Dibue et al. did. There is thus no justification to cite this publication. Given the misleading discussion here, a correction and clarification is requested for this part of the publication.

On 2015 Oct 30, Marco Weiergräber commented:

This review article is dealing in major parts with a comparison of the work of Münch et al., "Cav2.3 E-/R-type voltage-gated calcium channels modulate sleep in mice" (Somnologie, September 2013, Volume 17, Issue 3, pp 185-192) and Siwek et al. "The Cav2.3 R-type voltage-gated Ca2+ channel in mouse sleep architecture" (Sleep. 2014 May 1;37(5):881-92. doi: 10.5665/sleep.3652). Following the publication of Münch et al. (2013), our group has raised substantial criticism to their work. For detailed information see: Weiergräber: "How do Cav2.3 voltage-gated Ca2+ channels affect sleep architecture?" (Somnologie, December 2013, Volume 17, Issue 4, pp 304-306) and Weiergräber: "Cav2.3 R-type Ca2+ channels in mouse sleep architecture—an update." (March 2015, Volume 19, Issue 1, pp 61-62) and Weiergräber: "A scientific assessment of Cav2.3 voltage-gated Ca2+ channels in rodent sleep architecture." (Sleep. 2015 Mar 1;38(3):501-2. doi: 10.5665/sleep.4520).

We had identified major experimental and analytical drawbacks in the study of Münch et al. (2013) that require -to our opinion- a total reperformance of the small sleep study performed by Münch et al. (2013). The numerous fundamental deficiencies in Münch et al. (2013) are not listet here again. We strongly advice reading our aformentioned commentaries.

However, instead of reperforming their study, Schneider and Dibue replied that the different mouse models might account for the differences in sleep study results between the groups (Schneider and Dibue, Somnologie, December 2013, Volume 17, Issue 4, pp 307-308 and Schneider and Dibue, Sleep. 2015 Mar 1;38(3):499. doi: 10.5665/sleep.4518). Although scientific reality tells a different story, Schneider and Dibue continue to suggest that the Schneider model of Cav2.3-/- might be superior to the Miller model of Cav2.3-/- which we used. In our response (Weiergräber: "A scientific assessment of Cav2.3 voltage-gated Ca2+ channels in rodent sleep architecture." Sleep. 2015 Mar 1;38(3):501-2. doi: 10.5665/sleep.4520) we have clearly elaborated that this explanation which is again repeated here in this review does not hold true and has no scientific basis. The suggestion that Cav2.3 fragments in the Miller model could form functional channels is not only speculative, indeed, publications by Annette Dolphins group (e.g. Raghib et al., 2001) has shown that it simply does not occur. Although we have communicated this fact to the authors repetitively, they again ignore it and they also did not cite our commentaries which might have helped to avoid their misleading argumentation again.

In order to comment or review their data it's mandatory for Münch et al. (2013) to first reperform their experiments to acquire valid sleep data, second to analyze for compensatory mechanisms in their model (which we did in the Miller model, but they did not in their model, at least they did not report) and finally, the Schneider model has to be evaluated for potential N-terminal peptide fragments and their influence on Ca2+ channel physiology. Finally, the authors cite Dibue et al. (2014, Epilepsia). We have explained to the authors in detail (Weiergräber and Papazoglou, Epilepsia. 2015 Jul;56(7):1180-1. doi: 10.1111/epi.13041.) that the gamma data presented there are not valid as the analysis of gamma up to 500Hz is not possible with the transmitter type they used (a F20EET from DSI with 1-50Hz bandwidth and 250 Hz nominal sampling rate). The Nyquist-Shannon-limit does not allow for analysis of such high gamma as Dibue et al. did. There is thus no justification to cite this publication. Given the misleading discussion here, a correction and clarification is requested for this part of the publication.

On 2015 Nov 10, Marco Weiergräber commented:

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On 2015 Dec 07, Marco Weiergräber commented:

None

On 2015 Dec 28, Marco Weiergräber commented:

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