Fig. 8.

C9orf72 haploinsufficiency affects excitatory neurotransmission and network function. a–c Primary rat hippocampal neurons were transduced with non-targeting control miRNA (miRNA NTC) or C9orf72 miRNA (miRNA C9orf72) lentivirus at 5DIV and miniature excitatory postsynaptic current (mEPSC) traces were recorded from single neurons on 12–13DIV at a holding potential of –70 mV (–84 mV with liquid junction potential correction). a Representative current traces, b mEPSC interevent interval time and c mEPSC amplitude data are presented as cumulative probability and mean ± SEM of n = number of cells recorded n (cells) miRNA-NTC = 15, miRNA-C9 = 13 from three individual batches of neurons. Statistical significance was determined by unpaired two-tailed t test, ns (not significant), *P < 0.05. d–g Multi-electrode array (MEA) recordings to measure network activity were performed at 12–13DIV on hippocampal neuron cultures transduced with non-targeting control miRNA (miRNA-NTC) or C9orf72 miRNA (miRNA-C9) lentivirus at 5DIV. d Representative traces of a single array channel electrode recorded from miRNA NTC or miRNA C9-transduced neurons. Scale bars 5 s, 50 μV. Network activity characteristics were quantified by determining the e interburst interval of network bursts, f intra-network burst spiking frequency, g network burst length. Data are presented as mean ± SEM of n = number of MEA arrays, n (arrays) miRNA-NTC = 6, miRNA-C9 = 7 from 4 individual batches of neurons. Statistical significance was determined by unpaired two-tailed t test, ns (not significant), *P < 0.05