FIGURE 1.

Induction of Dkk1 induces 40% loss of inhibitory synapses in dorsal striatum. (A) Schematic representation of the generation of iDkk1 mice by the crossing of mice carrying the Dkk1 cDNA under the control of a doxycycline responsive promoter (tetO) with mice carrying the doxycycline-controlled transactivator 2 (rtTA2) downstream of the CaMKIIα promoter. In the absence of doxycycline (OFF), Dkk1 expression was not induced, whereas in animals fed with doxycycline (ON), Dkk1 is expressed, notably but not exclusively, in the dorsal striatum, the region under study here (red square on the sagittal brain scheme) in iDkk1 mice. (B) Confocal images from dorsal striatum show a dramatic reduction in inhibitory synapse number (white arrows) based on the co-localized pre- and postsynaptic markers; vGAT (green) and Gephyrin (red) puncta. The scale bars represent 2 μm; Dashed boxes correspond to enlarged areas depicted on the right-most panels, scale bar: 0.5 μm. (C) Forty percent of inhibitory synapses were lost in iDkk1 mice as shown on the quantification of pre- and postsynaptic markers and their co-localization. N = 5 mice per group; ^∗∗p < 0.01; ^∗∗∗p < 0.005, Mann–Whitney.