Basal level of network activity dictates direction of AM251 effect. A–C, Histograms of the effect of muscimol (A, n = 8), CTZ (B, n = 5), and 4-AP (C, n = 5) on spontaneous burst rates and of the effect of a subsequent application of AM251 (connected circles represent individual experiments). AM251 excited cultures with low basal burst rates (in muscimol), whereas it inhibited those with high basal burst rates (in CTZ and in 4-AP). D, Net effect of AM251 expressed as a function of basal burst rate. A significant inverse correlation was found when the data of all the AM251 experiments were pooled (n = 31). E, Histogram summarizing the effect of AM251 when inhibitory synaptic transmission was blocked. AM251 significantly increased bursting in Ptx (n = 6), had no effect in Ptx + CGP (n = 6), and significantly decreased bursting in Ptx + CGP + CTZ (n = 4). F, Net effect of AM251 expressed as a function of basal burst rate in disinhibited cultures. A significant inverse correlation was found when the data of all the AM251 experiments in disinhibited cultures were pooled (n = 16). Bold symbols with error bars represent the averages for their respective experimental conditions. Solid and dashed lines represent the linear regression and 95% confidence interval, respectively.