(A) Cumulative frequency histograms of amplitudes (normalized) of miniature spontaneous excitatory synaptic currents for control (CTR; left; 6 subjects; n>140 neurons per treatment), Angelman (AS; middle; 4 subjects; n>80 neurons per treatment), and Dup15q (right; 4 subjects; n>100 neurons per treatment) cultures. *P<0.0001 indicated significant differences between control and GABAzine treatments (Student’s t-test). (B) Example traces of miniature spontaneous excitatory synaptic currents from CTR, AS, and Dup15q neurons following treatment with either vehicle (left) or GABAzine (right). Scale bar: 10 pA, 100ms. (C) Cumulative frequency histograms of raw amplitudes of miniature spontaneous excitatory synaptic currents for 2 control subjects treated with TTX (Control 1; left. Control 2; middle), with baseline synaptic frequencies >3 Hz. Right: Cumulative frequency histograms of raw baseline (vehicle-treated) amplitudes for control, AS, and Dup15q cultures. *P<0.0001 indicates significant differences between control and Dup15q, #P<0.0001 indicates significant differences between control and AS (Kolmogorov-Smirnov test). (D) Example traces of spontaneous action potential firing from control (CTR) and Dup15q neurons from data presented in (E). Scale bar: 20 mV, 1s. (E) Spontaneous action potential (AP) firing rate of vehicle- or TTX-treated neuronal cultures from control and Dup15q subjects following washout of TTX. *P<0.05 indicates significant differences between vehicle- and TTX-treated cultures (Student’s t-test).