Fig. 5: Ulotaront reduces spontaneous firing in hippocampal CA1.

A−G Spontaneous firing in the CA1 recorded by multi-electrode array (MEA). Schematic of the mouse line (A, left), brain area (A, right), recording strategy (B) and experimental time course (C). Spontaneous neuronal firing activity was extracellularly recorded in the dorsal CA1 by means of a MEA. Firing rate was analyzed during pre-drug baseline condition and for the last 5 min of treatment with ulotaront (1 μM, 10 μM and 30 μM) or vehicle. D Left, Representative traces of spontaneous firing before (top) and during (middle) vehicle application, and upon TTX (bottom). Right, representative raster plots displaying the firing activity for the ulotaront groups (each line represents a spike). E Firing rate during baseline (b) and upon bath application (t) of ulotaront (1 μM, 10 μM, 30 μM) or vehicle. F, G Effect of treatment with vehicle control vs ulotaront on firing rate. Data were normalized to baseline and presented as average time course (F) as well as summary plot (G; each dot represents an electrode, as in (E)). H−L Spontaneous firing in the CA1 recorded by micropipette. H, I Recording strategy (H) and experimental time course (I). Extracellular single-unit recordings were acquired by means of a micropipette positioned in the stratum pyramidale of the CA1. Firing rate was analyzed during pre-drug baseline condition and for the last 5 min of treatment with 30 μM ulotaront or vehicle. J Representative raster plots displaying the spontaneous firing for the vehicle (top) and ulotaront (bottom) groups. K−M Analysis on firing rate recorded by micropipette, corresponding to (E−G). In (K) and (M), each dot represents a unit. Data are mean ± s.e.m; n = 27−45 electrodes, 9−16 cells. Statistics are described in Table S1. ns, not significant; **p < 0.01; ****p < 0.0001.