Imbalanced expression of clustered protocadherins in pre- and post-synaptic compartments of CA1 pyramidal cells during hippocampal development

SUMMARY Clustered protocadherins (cPcdhs) are candidates for the neural circuit formation; however, the localization of cPcdhs in pre- and post-synaptic compartments has not been well characterized. Here we examined the localization of cPcdhγ proteins in the mouse hippocampal CA1 region using light and electron microscopy. From postnatal day 7 to 21, cPcdhγ immunosignals were detected in approximately 40–60% of spines of pyramidal cells. SDS-digested freeze-fracture replica labelling revealed that cPcdhγ immunolabeling was found in 50% of PSD 95-positive postsynaptic profiles but only in less than 10% of vGluT1-positive pre-synaptic terminals. Interestingly, cPcdhγ-positive pre-synaptic terminal was exclusively accompanied by cPcdhγ-positive postsynaptic counterpart. In addition, electrophysiological investigations revealed that the miniature excitatory postsynaptic current frequency in cPcdhγ cKO mice was significantly higher than that in wild-type mice. These results suggest that cPcdhγ proteins are unequally distributed in the pre- and post-synaptic membrane during neural circuit development and regulate the number of excitatory synapses.