FBS Colloquia No.163KOKORO-Biology Group

Influence of the postnatal experience on the cortical neural connections predetermined by the gene-regulation during embryonic development.

In the neocortex, each neuron connects to a relatively small number of neighboring neurons in a highly specific manner to form a functional microcircuit. Here we show that neurons within the same layer establish cell-lineage-dependent reciprocal connections. To visualize clonal neurons, we generated chimeric mice by injecting induced pluripotent stem cells (iPS cells) marked with a fluorescent protein into wild-type mouse blastocysts. We then conducted dual whole-cell recordings from presumed clonal or non-clonal neuron pairs within a layer 4 barrel in cortical slices. We observed a transient increase in synaptic connections between clonal but not nonclonal neuron pairs during postnatal development, followed by selective stabilization of the reciprocal connections between clonal neuron pairs. This high degree of reciprocity of connections between clonal cells was abolished in clonal cells lacking DNA methyltransferase 3b (Dnmt3b) and also in clonal neurons lacking clustered protocadherins (cPcdhs); individual neurons express various isoforms of these cell-adhesion proteins, in a Dnmt3b-dependent manner. Our findings suggest that the Dnmt3b-mediated epigenetic regulation of cPcdh expression enables clonal neurons to establish cell-lineage-specific connections during postnatal development.