Fig. 3: The targeted deletion of Trio in INs leads to reduced densities of cortical deep layer PV-expressing INs and of superficial layer CR and VIP-expressing INs in the post-natal somatosensory cortex, resulting in reduced cortical inhibition.

A–D Reduced density of GABAergic INs in the somatosensory cortex of Trio^cKO mice at P21. Examples of coronal brain sections showing fate-mapped GABAergic INs (GFP, green) and DAPI counterstaining (blue) at P21 in the somatosensory cortex of Trio^WT (A) and Trio^cKO (B) mice. C, D Histograms showing the quantifications of fate-mapped GABAergic INs at P21 in the mouse somatosensory cortex. E–T Reduced density of deep layer PV-expressing INs and superficial layer CR- and VIP-expressing INs, but not SST-expressing INs, in the somatosensory cortex of Trio^cKO mice at P21. Immunofluorescence for PV (E, F), SST (I–J), CR (M, N) and VIP (Q, R) (red) with DAPI counterstaining (blue) and fate-mapped GABAergic INs (GFP, green) in the Trio^WT (E, I, M, Q) and Trio^cKO (F, J, N, R) somatosensory cortex at P21. Histograms of corresponding quantifications are shown for PV⁺GFP⁺ INs (G, H), SST⁺GFP⁺ INs (K, L), CR⁺GFP⁺ INs (O, P) and VIP⁺GFP⁺ INs (S, T) (n = 10 Trio^WT and 10 Trio^cKO brains for GFP quantifications; n = 8 Trio^WT and 7 Trio^cKO brains for PV quantifications; n = 4 Trio^WT and 4 Trio^cKO brains for SST and CR quantifications and n = 3 Trio^WT and 3 Trio^cKO brains for VIP quantification). U–X Reduced cortical inhibition in Trio^cKO mice. Representative electrophysiological traces of sIPSCs in acute slices from Trio^WT (U) and Trio^cKO (V) mice. Histograms showing the frequency (W) and amplitude (X) of sIPSCs (n = 13 cells from 4 Trio^WT brains and 12 cells from 4 Trio^cKO brains). *P < 0.05, ***P < 0.001 and ****P < 0.0001, by two-way ANOVA followed by Bonferroni’s multiple comparisons test (C, G, K, O, S) or by Mann–Whitney test (D, H, L, P, T, W, X). Scale bar: 200 µm (N).