(A-C) Global normalization of DSCAM gene dosage in Ts65Dn mice. mIPSCs were recorded from brain slices from euploid, Ts65Dn, and Ts65Dn:DSCAM+/+/− mice, which were obtained by mating female Ts65Dn and male DSCAM2j mice. (A) Representative traces of mIPSCs from PyNs in layer II/III of the ACC. (B, C) Quantification of mIPSC frequency (B) and amplitude (C). A total of 6 euploid control, 6 Ts65Dn, and 6 Ts65Dn:DSCAM+/+/− mice were analyzed. For each mouse, 2–4 PyNs were recorded. (D-F) Normalization of DSCAM gene dosage in GABAergic neurons in Ts65Dn mice. Lhx6-Cre mice were crossed with DSCAMflox mice to generate Lhx6-Cre:DSCAMflox mice in the Ts65Dn background (Ts65Dn:Lhx6-Cre:DSCAMflox). (D) Representative traces of mIPSCs from PyNs in layer II/III of the ACC in euploid:Lhx6-Cre, Ts65Dn:Lhx6-Cre, and Ts65Dn:Lhx6-Cre:DSCAMflox brain slices. (E, F) Quantification of mIPSC frequency (E) and amplitude (F). A total of 4 euploid control, 4 Ts65Dn, and 4 Ts65Dn:Lhx6-Cre:DSCAMflox mice were analyzed. For each mouse, 2–4 PyNs were recorded. One-way ANOVA for multigroup comparisons and post hoc Student t tests for pair-wise comparisons. **: p < 0.01; ***: p < 0.001; ns: not significant (p > 0.05). The data underlying this Figure can be found in https://doi.org/10.5281/zenodo.7714234. ACC, anterior cingulate cortex; DSCAM, Down syndrome cell adhesion molecule; mIPSC, miniature inhibitory postsynaptic current; PyN, pyramidal neuron.