Neural Plasticity / 2016 / Article / Fig 2

Research Article

Miglustat Reverts the Impairment of Synaptic Plasticity in a Mouse Model of NPC Disease

Figure 2

Synaptic plasticity in CA1 hippocampal subfield of WT and NPC1−/− mice. (a) % PS amplitude as a function of time is shown after tetanic stimulation applied at time (arrow). The PS amplitude, measured every minute, corresponds to an average of 6 recordings/min. Points in the plot are means ± SEM of values obtained from different slices. Note the impairments of both the induction and the expression of LTP in NPC1−/− untreated mice (white rombs, ) in comparison to the WT (black circles, ) untreated mice. (b) Recordings were obtained from different slices of WT (A) and NPC1−/− untreated (B), WT saline (C) and NPC1−/− saline treated (D), and WT Miglustat (E) and NPC1−/− Miglustat (F) treated mice. The first curve of each group refers to the BST and it was recorded before the application of the tetanic stimulation, while the other curves refer to population spikes at times 1, 10, 20, and 60 min after the HFS. (c) % PS amplitude after HFS as a function of time is shown in WT untreated (horizontal pattern bar, ), in WT saline treated (black bar ), in WT Miglustat treated (diagonal pattern bar, ), in NPC1−/− untreated (vertical pattern bar, ), in NPC1−/− saline treated (grey bar, ), and in NPC1−/− Miglustat treated (white bar, ) mice slices at minutes 1, 10, 20, and 60. Bars in the plot are means ± SEM of values obtained from different slices. Note significant statistical differences in PS amplitude during 1-hour recording in NPC1−/− untreated versus WT untreated mice slices: PTP and LTP values at 10, 20, and 60 min after tetanic stimulation were, respectively, 221.8 ± 42.5, 137.3 ± 11, 117.8 ± 14, and 103.3 ± 20.9 versus 323.8 ± 29.8, 250.2 ± 29.9, 222 ± 31.9, and 195.6 ± 29.8 ( at 1 and 60 min; at 10 and 20 min). A statistically significant difference is also present in NPC1−/− Miglustat treated versus NPC1−/− saline treated mice slices: the values recorded were 355.7 ± 46.8, 295.8 ± 30.5, 249.4 ± 29, and 211.1 ± 29.1 versus 216.7 ± 40.4, 130.3 ± 12.4, 120.8 ± 13.5, and 108.3 ± 21.4 ( < 0.05 at 1 min; < 0.01 for all the following minutes).
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