https://padlet.com/darrengoffin1/h3exg5u6yd09x5i3 Synaptic Basis of Rett Syndrome en-us 2022-02-22 08:09:36 UTC 2022-03-01 13:50:10 UTC hello@padlet.com https://padlet.net/icons/png/1f9e0.png aw17141 https://padlet.com/darrengoffin1/h3exg5u6yd09x5i3/wish/2071423369 1. Results suggest that the mutation of the phosphorylation sites on MeCP2 impacts the size of the readily releasable pool. Panel A shows this as the application of TTX to the mutant cells leads to less-frequent mEPSCs compared with WT cells treated with TTX that show a higher frequency of mEPSCs. ]]> 2022-03-01 13:22:07 UTC https://padlet.com/darrengoffin1/h3exg5u6yd09x5i3/wish/2071423369 aw17141 https://padlet.com/darrengoffin1/h3exg5u6yd09x5i3/wish/2071426332 2. the other results show that the amplitude of EPSCs isn't significantly different between WT and mutant conditions, which suggests that the differences in frequency of EPSCs recorded in panel A between controls and mutants are due to a difference in the readily releasable pool rather than any difference in the amount of NT released - this suggests that removing phosphorylation sites S421 and S424 from MeCP2 may impact the size of the RRP in Rett-like phenotypes]]> 2022-03-01 13:23:46 UTC https://padlet.com/darrengoffin1/h3exg5u6yd09x5i3/wish/2071426332 https://padlet.com/darrengoffin1/h3exg5u6yd09x5i3/wish/2071438360 They have not shown any statistical analysis on frequency graphs, so can’t make any conclusions from this data ]]> 2022-03-01 13:30:27 UTC https://padlet.com/darrengoffin1/h3exg5u6yd09x5i3/wish/2071438360 aw17141 https://padlet.com/darrengoffin1/h3exg5u6yd09x5i3/wish/2071438425 3. Biccuculine appears to have no impact on the mutant cultured MeCP2 neurons, unlike in the WT conditions which suggests that GABA receptors specifically are impacted in mutant MeCP2 neurons, following removal of the phosphorylation sites]]> 2022-03-01 13:30:29 UTC https://padlet.com/darrengoffin1/h3exg5u6yd09x5i3/wish/2071438425 https://padlet.com/darrengoffin1/h3exg5u6yd09x5i3/wish/2071442032
The WT and the mutant cells display the same response to TTX, indicating that there is no changes in the properties of the VGSC in the mutant. There is however a difference in how both cell types respond to Bicuculline, a competitive GABA antagonist. The mutant cells do not show a significant difference between the control and the Bic solution, indicating a potential change in structure of the GABA receptors. This is not seen in the WT cells, which show a significant difference in mEPSCs amplitude. Both cell types in all conditions do not display any differences in the frequencies of mEPSCs. This data does not indicate significant differences between cell groups, which can only be inferred. The data would be improved if this was included. The probability graphs would also benefit from significance denotations, making it easier to read. The large n number used is a positive for this figure.

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•      The figure reports a significant difference in fluorescence of GluA2 in WT neurons treated with control solution vs. WT neurons treated with TTX and separately, Bic. The authors report a significant increase in the quantified fluorescence of GluA2 in TTX-treated WT neurons and a significant decrease in quantified fluorescence of Bic-treated WT neurons. By comparison, the mutant-KI mice exhibit a significant increase in GluA2 expression when treated with TTX but show no significant decrease in GluA2 expression when treated with Bic. The same patterns described are shown in K-L in the WT and mutant-KI neurons. 

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•      These results support the findings of the first experiment and suggest that removing MeCP2 phosphorylation impacts synaptic downscaling in neurons but has no effect on synaptic upscaling. The results are problematic however as it is not possible to quantify fluorescence between slices because of the countless potential confounds leading to different levels of fluorescence and the authors fail to state which statistical test they used, making it difficult to judge the reliability of the figure 

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