Figure 6. KCTDs modulate release probability of ventral MHb terminals.

(A) In whole-cell recordings from rostral IPN neurons, paired-pulse ratios (PPR) of electrically evoked glutamatergic excitatory postsynaptic currents (EPSCs) were significantly lower in KCTD12b KO mice compared with WT, KCTD8 KO, and KCTD8/12b double KO mice; **p<0.01, ***p<0.001, Kruskal–Wallis with Dunn’s post hoc test. (B–D) Example variance-mean measurements of electrically evoked EPSC amplitudes at varying external Ca²⁺ concentrations in recorded in rostral IPN neurons of WT (B), KCTD8 KO (C), and KCTD12b KO mice (D). (E) Quantification of release probability (left graph) and quantal size (right graph) indicates significantly reduced release probability in KCTD8 KO mice and increased release probability in KCTD12b KO mice. Quantal size remained unaffected. *p<0.05, ***p<0.001, ****p<0.0001 one-way ANOVA with Tukey’s post hoc test. (F) WT animals were injected with lentivirus expressing either EGFP (WT LV-EGFP) or KCTD8/EGFP (WT LV-KCTD8) into the MHb. Left: Example images of acute IPN slices after electrophysiological recordings showing EGFP signal in fibers inside the IPN. Right: Overexpression of KCTD8 resulted in significantly lower PPR values compared with EGFP controls **p<0.01, unpaired t-test. (G) Left: Lentiviral expression of EGFP or KCTD12b/EGFP in acute slices of KCTD12b KO mice. Right: Lentiviral expression of KCTD12b significantly increased PPR values compared with EGFP controls **p<0.01, unpaired t-test. See also Figure 6—figure supplement 1.

Figure 6—figure supplement 1. Baclofen still potentiated release in all KCTD KO lines.

(A) Example time courses of GBR-mediated potentiation in WT, KCTD8 KO, KCTD12b KO, and KCTD8/12b dKO mice. (B) Average time course of baclofen-mediated EPSC enhancement.