Fig. 8.

TRVA242 restores synaptic defects at the NMJ in zebrafish models of ALS. Recordings of mEPCs, which result from spontaneous release of quanta, were done on wt TDP-43, mut-TDP-43, and mut TDP-43 + TRVA242 (5 μM), wt SOD-1, mut SOD-1, mut SOD-1 + TRVA242 (5 μM) at 48 hpf. mut-TDP-43 larvae showed a significantly reduced amplitude (A, B) and frequency (C) compared to wt TDP-43 larvae. Treatment with TRVA242 significantly restored the amplitude and frequency. D decay constant and E rise time were measured across all treatment groups and no significant differences were found. mut-SOD-1 larvae showed no significant differences in amplitude (F), decay constant (G), and rise time (H). mEPC frequency(I) of mut SOD-1 larvae were significantly increased compared to wt TDP-43 larvae. Treatment with TRVA242 significantly restored values to wt TDP-43 levels. Representative mEPC recordings (J) from wt SOD-1, mut SOD-1, mut SOD-1 + TRVA242 (5 μM) larvae for 3 min. Number in parentheses indicates sample sizes. Data are expressed as mean ± SEM, **p < 0.01. Broken lines in the figures represent the effect of pimozide at 20 μM (positive control)