Fig. 6: SR-1815, a proof-of-concept small molecule, resolves elevated synaptic function and increased neuronal activity in Syngap1 haploinsufficient neurons.

a) Representative traces from mEPSC recordings in Syngap1^+/+ (blue) and Syngap1^+/- (red) neurons treated with vehicle or SR-1815 (left). Plot showing mEPSC frequency for the four different conditions (middle) and mEPSC amplitudes for the four different conditions (right) n = 17 for Syngap1^+/+: vehicle; n = 16 for Syngap1^+/+: SR-1815; n = 17 for Syngap1^+/-: vehicle; n = 18 for Syngap1^+/-: SR-1815. Error bars represent SEM. b Syngap1 + /+ and Syngap1 + /- neurons transduced with AAV9 vectors expressing Flex-gCAMP8f and Cre (to control labeling). Neurons were treated with DMSO or 1.5 μM SR-1815 for 14 days. Calcium imaging performed on DIV14. Plot showing the spiking frequency (spikes per second) for the four different conditions. For DMSO control 12 fields were imaged for Syngap1^+/+ Syngap1^+/- and for SR-1815 respectively 14 and 17 fields for Syngap1^+/+ Syngap1^+/- were imaged from at least 4 wells per conditions. The total number of segmented neurons were DMSO Syngap1^+/+, n = 1693; Syngap1^+/-, n = 2047; SR-1815 Syngap1^+/+, n = 1803 and Syngap1^+/-, n = 1253. Dots with error bar represent mean and SEM, individual neuron value (small dot) and well average (large dot) are plotted, within the violin plot median, 25th and 75th percentile. p-value for main effects and interaction are indicated as n.s.: p  >  0.05, *p  <  0.05, **p  <  0.01, ***p  <  0.001, ****p  <  0.0001, detailed statistics and source data are provided as a Source Data file.