CSMD3 Deficiency Leads to Motor Impairments and Autism-Like Behaviors via Dysfunction of Cerebellar Purkinje Cells in Mice

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Figure 8.
Figure 8.

CSMD3-deficient mice display abnormal synaptic transmission and maladaptive synaptic plasticity in the cerebellum. A–C, Whole-cell voltage-clamp recording of mEPSCs in cerebellar PCs. A, Representative mEPSC traces in the wild-type (top) and CSMD3−/− (bottom) mice. Calibration: 10 pA, 1 s. Right, Examples of enlarged mEPSC trace. Calibration: 5 pA, 20 ms. B, Cumulative distribution of mEPSC amplitude and plotted averaged amplitudes (inset bar graphs) from each recorded PC (n = 16 cells from 4–5 mice/group; t(29) = 2.70, p = 0.0114). C, Same as B, but for instantaneous frequency of mEPSC (n = 15–16 cells from 4–5 mice/group; t(29) = 3.08, p = 0.0045). D–F, Whole-cell voltage-clamp recording of mIPSCs in cerebellar PCs. D, Representative mIPSC traces in the wild-type (top) and CSMD3−/− (bottom) mice. Calibration: 20 pA, 1 s. Right, Examples of enlarged mIPSC trace. Calibration: 10 pA, 20 ms. E, Cumulative distribution of mIPSC amplitude and plotted averaged amplitudes (inset bar graphs) from each recorded PC (n = 15–16 cells from 4 mice/group; t(29) = 1.61, p = 0.1182). F, Same as E, but for mIPSC instantaneous frequency (n = 15–16 cells from 4 mice/group; t(29) = 1.58, p = 0.1253). G–I, LTD of EPSCs at PF–PC synapses recorded from the wild-type and CSMD3−/− mice. G, H, Representative traces of EPSC and the time course of changes in normalized EPSC amplitudes (percentage of baseline). G, Representative traces of EPSC just before (left) and after (right) conjunctive stimulation in the wild-type (top) and CSMD3−/− (bottom) mice. Calibration: 100 pA, 20 ms. I, Bar graph for the averaged EPSC amplitudes (normalized to baseline) during 40 min after conjunctive stimulation (n = 5 cells from 3–4 mice; t(8) = 5.24, p = 0.0008). All EPSC amplitudes were normalized to baseline in percentiles. Data are presented as the mean ± SEM. **p < 0.01, ***p < 0.001; n.s., no statistical difference, compared between the wild-type and CSMD3−/− groups; two-tailed unpaired t test (B, C, E, F, I).

  1. The Journal of Neuroscience vol. 43 no. 21 3949-3969
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