Distinct molecular programs regulate synapse specificity in cortical inhibitory circuits

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Science  25 Jan 2019:
Vol. 363, Issue 6425, pp. 413-417
DOI: 10.1126/science.aau8977

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Inhibitory synapse specificity

As neurons build circuits in the developing brain, they select not only what other neurons to connect to but also where on that neuron they will touch base. Working in mice, Favuzzi et al. found that gene expression programs that define subsets of interneurons also define where on the postsynaptic partner those interneurons prefer to build a synapse. One class of interneurons prefers to synapse onto the cell body of pyramidal neurons, another class onto the dendrites, and yet another onto the axon initial segment.

Science, this issue p. 413


How neuronal connections are established and organized into functional networks determines brain function. In the mammalian 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 toward parsing interneuron diversity, yet the molecular mechanisms by which interneuron-specific connectivity motifs emerge remain unclear. In this study, we investigated transcriptional dynamics in different classes of interneurons during the formation of cortical inhibitory circuits in mouse. We found that whether interneurons form synapses on the dendrites, soma, or axon initial segment of pyramidal cells 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.

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