![]() ![]() Males (n = 22) and females (n = 11) TDP mice on a congenic C57BL/6J genetic background were monitored for mortality. ( d) Intracellular application of picrotoxin (PTX, 350 μM) enhanced AP firing of L5-PNs from both TDP and WT mice, and abolished the AP firing differences between TDP and WT mice. Bottom: quantitative analyses of amplitude (WT, 11.3 ± 0.7 pA TDP, 11.5 ± 0.9 pA Mann-Whitney U-test, p = 0.99, z(42) = 0.01) and frequency (WT, 5.6 ± 0.5 Hz TDP, 5.9 ± 1.1 Hz Mann-Whitney U-test, p = 0.47, z(42) = 0.72) of mEPSC (WT and TDP, n = 24 and 20 neurons, 3 mice each group). ( c) mEPSC was similar in 3-week-old TDP and WT littermate controls. Right: quantitative analyses of puncta densities ( TDP-43::YFP, 79.5 ± 6.0% of YFP controls, unpaired t-test, p = 0.0326, t(85) = 2.173 n = 45, 42 neurons from 4 mice each group). Left: representative overlaid (Red, VGAT Green, YFP) and separated images of VGAT staining alone (scale bar represents 5 μm). TDP mice were crossed with Thy1-YFPH ( YFP) mice to label L5-PNs and GABAergic synapses were identified through immunostaining of presynaptic vesicular GABA transporter (VGAT). ( b) TDP mice (3 weeks age) showed reduced GABAergic synapse densities around somatic areas of L5-PN. Right: quantitative analysis of the amplitude (WT, 5.1 ± 0.3 nA TDP, 3.1 ± 0.4 nA Mann-Whitney U-test, p = 0.0007, z(20) = 2.6) of the maximal response of eIPSC (WT and TDP, n = 11 neurons, 3 mice each group). Left: overlay of the average of maximal response of eIPSC recorded from WT and TDP mice. ( a) L5-PNs in TDP mice (3 weeks age) exhibited significantly reduced eIPSC. Kaur, P., Karolina, D.S., Sepramaniam, S., Armugam, A. Yang, G., Pan, F., Parkhurst, C.N., Grutzendler, J. Zhang, W., Peterson, M., Beyer, B., Frankel, W.N. Pfeffer, C.K., Xue, M., He, M., Huang, Z.J. Wegorzewska, I., Bell, S., Cairns, N.J., Miller, T.M.
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