Imbalanced expression of clustered protocadherins in pre- and post-synaptic compartments of CA1 pyramidal cells during hippocampal development
Imbalanced expression of clustered protocadherins in pre- and post-synaptic compartments of CA1 pyramidal cells during hippocampal development
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DOI：
10.1101/2023.04.15.536995
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发表时间：
2023-04
期刊：
影响因子：
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通讯作者：
Etsuko Tarusawa;Saki Hasegawa;Daisuke Noda;Nanami Kawamura;Y. Fukazawa;Masahiko Watanabe;T. Hirabayashi;Takeshi Yagi
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文献类型：
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作者：
Etsuko Tarusawa;Saki Hasegawa;Daisuke Noda;Nanami Kawamura;Y. Fukazawa;Masahiko Watanabe;T. Hirabayashi;Takeshi Yagi
神经回路形成的候选人，然而，在突触前和突触后的车厢cPcdhs的本地化还没有得到很好的表征。我们在光镜和电镜下观察了小鼠海马CA 1区cPcdhγ蛋白的定位。生后7 ~ 21天，在锥体细胞棘中约有40-60%表达cPcdhγ免疫信号。SDS消化的冷冻断裂复制标记显示，在50%的PSD 95阳性突触后轮廓中发现cPcdhγ免疫标记，但仅在不到10%的vGluT 1阳性突触前终末中发现cPcdhγ免疫标记。有趣的是，cPcdhγ阳性的突触前终末只与cPcdhγ阳性的突触后终末相伴随。此外，电生理研究显示，cPcdhγ cKO小鼠的兴奋性突触后微电流频率显著高于野生型小鼠。这些结果表明，在神经回路发育过程中，cPcdhγ蛋白在突触前膜和突触后膜中分布不均匀，并调节兴奋性突触的数量。
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.