https://padlet.com/darrengoffin1/df3tbxaisw62dxia Autism en-us 2022-03-07 15:50:36 UTC 2026-01-30 23:32:04 UTC hello@padlet.com https://padlet.net/icons/png/1f9e0.png https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082015766
TSC is caused by heterozygous mutations in TCS1 and TCS2 genes, hence mirroring the effects of the disease (homozygous may be lethal). TCS2 was chosen over TCS1 because its more common and causes more severe phenotypes in humans.

]]> 2022-03-07 16:15:57 UTC https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082015766 https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082016996 The disease is caused by heterozygous mutations in the genes encoding Tsc2, so in order to mimic the disease in mice, you also need a heterozygote.

]]> 2022-03-07 16:16:30 UTC https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082016996 https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082027245 In addition, Tsc2-/- mice embryos die from hepatic hypoplasia. ]]> 2022-03-07 16:20:31 UTC https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082027245 https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082047679 LTD was determined by measuring the slopes of fEPSPs in DHPG induced LTD, synaptically induced (through paired pulses) pre-synaptic LTD and NMDAR dependent LTD. Also by phosphorylation and activation of ERK 1/2]]> 2022-03-07 16:29:56 UTC https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082047679 https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082051501 The initial slope of the response was used to assess changes in synaptic strength.
The latency at which the peak amplitude occurs is often, if not always, contaminated by the population spike reflected from the somata, and thus is a mixture of synaptic and non-synaptic currents. The rising slope is always used because it occurs before the population spike arrives back in the dendrites, and thus is an uncontaminated reflection of the synaptic current (and is proportional to the amplitude of that synaptic current). ]]> 2022-03-07 16:31:37 UTC https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082051501 https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082067323 It is an NMDAR antagonist that was used to show that the reduction in LTD was not due to NMDAR, just mGluR]]> 2022-03-07 16:38:48 UTC https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082067323 https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082072584
10 WT brain slices from 5 animals and 12 Tsc2+/- brain slices from 6 mice were used. mGluR-LTD was induced by delivering 2 electrophysiological pulses at 1Hz for 20 minutes using electrodes. Bathed in DHGP – a glutamate receptor agonist – they measured and compared fEPSP slope (change in measured EPSPs) for both WT and mutant slices following this stimulation to assess whether LTD was significantly different for mutant mice compared with WT. In a control experiment, the authors showed that NMDAR-dependent LTD is no different between groups.

]]> 2022-03-07 16:41:12 UTC https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082072584 https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082095813 In figure 1A,the LTD is induced through GHPG, an agonist of GluR. To check if the change is also due to NMDAR they repeated the experiment with the NMDAR antagonist D-AP5 and they used an electrically induced NMDAR dependant LTD (Fig 1B). This showed no difference from F1A, so there is no dependance on NMDAR. ]]> 2022-03-07 16:52:34 UTC https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082095813 https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082096575 There is no change between fEPSPs in NDMAR dependant LTD. However there is no evidence that the LFS they use is causing NMDAR dependent LTD.]]> 2022-03-07 16:52:57 UTC https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082096575 https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082098460 A ttest is the right statistical test but they don't mention the one they used for panels A-C]]> 2022-03-07 16:53:49 UTC https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082098460 https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082107817 In figure 1d, there is no difference between WT and mutant ERK phosphorylation, this shows that the phosphorylation by mGluR is not affected. There is also found to be a decrease in translation of the proteins required to stabilise LTD, like Arc]]> 2022-03-07 16:58:28 UTC https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082107817 https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082113479
CDPPB is a positive allosteric modulator – it is a drug that binds on the regulatory (non-active) site of the mGluR enzyme and potentiates its physiological activation without activating it directly, or behaving like a receptor agonist. By binding elsewhere than the active site, CDPPB makes activation of the receptor more likely and potentiates this process in order to increase mGluR activation. 

]]> 2022-03-07 17:01:17 UTC https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082113479 https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082115306 They examined DHPG induced phosphorylation of ERK1/2 as a measure for mGluR signalling. They found that both basal ERK1/2 phosphorylation and DHPG induced increases in ERK1/2 phoshorylation are unaltered in Tsc2+/- mice, suggesting that the deficit in mGluR-LTD in the Tsc2+/- hippocampus is not due to dysregulation of Gp 1 mGluR signalling.]]> 2022-03-07 17:02:15 UTC https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082115306 https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082116167 It is a MGluR positive modulator that binds the allosteric site. It does not activate MGluR directly but facilitates its activation]]> 2022-03-07 17:02:40 UTC https://padlet.com/darrengoffin1/df3tbxaisw62dxia/wish/2082116167