Distinct molecular programs regulate synapse specificity in cortical inhibitory circuits

How neuronal connections are established and organized in functional networks determines brain function. In the mouse cerebral cortex, different classes of GABAergic interneurons exhibit specific connectivity patterns that underlie their ability to shape temporal dynamics and information processing. Much progress has been made parsing interneuron diversity, yet the molecular mechanisms by which interneuron subtype-specific connectivity motifs emerge remain unclear. Here we investigate transcriptional dynamics in different classes of interneurons during the formation of cortical inhibitory circuits. We found that whether the interneurons synapse with pyramidal neurons on their dendrites, soma, or axon initial segment is determined by synaptic molecules that are expressed in a subtype-specific manner. Thus cell-specific molecular programs that unfold during early postnatal development underlie the connectivity patterns of cortical interneurons. RNAseq of three different subtypes of GABAergic inhibitory neurons (SST+, PV+ and Chandelier cells) at two developmental stages (P5 and P10) from mouse cortical regions as well as three control populations: interneurons at P0, pyramidal excitatory neurons at P12 and PLP+ oligodendrocytes at P10.