Supplementary Figure 12: Impairments of mRNA transport and long-term potentiation in Disc1^−/− mice.

(a) Dendritic localization of ITPR1 3' UTR in organotypic slices from wild-type and Disc1^−/− mice. Hippocampal slices (slice thickness, 250 μm) were prepared from wild-type and Disc1^−/− mice at 6 postnatal days. After 3 d in culture, the plasmids were introduced into the slices by biolistic transfection. The transport distances of Venus–ITPR1 3' UTR were measured in the DNA-transfected neurons of slices at 2 d after transfection. The blue bars indicate the distance between the soma and the farthest transported granules containing ITPR1 3' UTR. Scale bars, 15 μm. (b) Relative frequency of the transport distance of ITPR1 3' UTR–containing granules. The transport distances of ITPR1 3' UTR granules were categorized into five groups. The data in b are from three independent experiments for each treatment and at least ten neurons per experiment (n = 30). Significant differences between the transport distances were determined by one-way ANOVA with Bonferroni post hoc test (wild-type versus Disc1^−/−, P < 0.01, F(1, 58) = 33.81). Bars show mean ± s.e.m. (c,d) The late phase of LTP (L-LTP) in the dentate gyrus of hippocampal slices from wild-type and Disc1^−/− mice (C57BL/6J, 3 weeks in age). (c) Ten trains of tetanic stimulation (100 Hz for 100 pulses with 60-s intervals; indicated by arrow) elicited L-LTP that persisted for at least 3 h in wild-type mice (137.3% ± 8.2% of baseline 180 min after the tetanic stimulation, n = 4). In Disc1^−/− mice, a potentiation of comparable magnitude was observed after the tetanic stimulation but declined to near-baseline level by 3 h (100.0% ± 6.3% of baseline 180 min after the tetanic stimulation, n = 4). The data are expressed as the mean ± s.d.(d) LTP amplitude was averaged at 30 min and 180 min after high-frequency stimulation in c and was expressed as a percentage of the baseline value. For statistical analysis we used the Mann-Whitney U-test (LTP amplitude: wild-type versus Disc1^−/− at 30 min, n = 4; wild-type versus Disc1^−/− at 180 min, n = 4). *P < 0.05. Bars show mean ± s.d.