Fig. 5: Expression of Tcf7l2 in midbrain is required for mouse USV production and TCF7L2 loss leads to impairment of synaptic transmission in PAG. | Molecular Psychiatry

Fig. 5: Expression of Tcf7l2 in midbrain is required for mouse USV production and TCF7L2 loss leads to impairment of synaptic transmission in PAG.

From: TCF7L2 acts as a molecular switch in midbrain to control mammal vocalization through its DNA binding domain but not transcription activation domain

Fig. 5

a The RiboTag mice (PMID: 19666516) were crossed to Vglut2-Cre/+ mice to label Vglut2-positive neurons in midbrain PAG. Neurons with TCF7L2 immunoreactive nuclear signals were positive for RPL22-HA cytosolic signals in PAG at P7 (bottom). Scale bar, 500 μm (top) and 50 μm (bottom). L, lateral; D, dorsal; V, ventral; ICe, external cortex of the inferior colliculus. PAG and ICe was shaped by dashed lines. b A schematic diagram for Tcf7l2 KO in PAG by AAV-Syn-mCherry-Cre injection. The AAV viral particles were injected into PAG of Tcf7l2 exon11 fl/fl mouse at P17 and USVs were measured at 3-month of age. The Cre expression was driven by a neuronal Syn1 promoter. AAV-Syn-mCherry served as a control. c Immunostaining results show that Tcf7l2 was conditional KO by AAV-Syn-mCherry-Cre in PAG region. d–g Key features of USVs measured from Tcf7l2 conditional KO mice that were injected with virus at P17. h Summary of GSEA analysis in PAGs at P7 between exon11 fl/fl and exon11 fl/fl;Vglut2-Cre/+ mice. NES, normalized enrichment score. i, j Representative mEPSC and mIPSC trace recording from LPAG of + /- and + /+ mice at one-month of age and statistic analysis of the amplitudes and frequencies. In d, e, f and g, the value are presented as mean ± SD. N.S., no significant difference, *p < 0.05, **p < 0.01, ***p < 0.001, t-test or ANOVA, SPSS. In d–g, mCherry (n = 6); mCherry-Cre (n = 12); in i, j, for mEPSC, +/+, n = 21/3; +/-, n = 23/3; for mIPSC, +/+, n = 22/4; +/-, n = 29/3.

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