Thread by @MarinLab

1/8 Are all synapses created equal? @clembrnrd in @Rico_lab and @MarinLab has found that the building of new synapses is controlled in a cell-type and even synapse-type-specific manner. This is the story @ScienceMagazine science.org/doi/10.1126/sc… ⬇ thread @dev_neuro @MRC_CNDD

2/8 We approached this question by investigating the wiring of PV+ and SST+ interneurons in the mouse neocortex. These cells have highly related developmental trajectories but play very different roles in adulthood, making them an attractive model for studying synapse specificity

3/8 We found that the mTORC1 inhibitor Tsc2 is required in PV+ but not SST+ interneurons to develop excitatory synapses targeting these cells. Notably, Tsc2 is not needed to make PV+ inhibitory output synapses: its function in this context is cell-type and synapse-type-specific.

4/8 How is this achieved? We identified a signalling pathway unique to PV+ cells that regulates the formation of the excitatory inputs they receive: Tsc2 regulation by the receptor tyrosine kinase ErbB4 enables the synthesis of specific proteins required for synapse formation.

5/8 We demonstrate that several proteins required for building excitatory synapses onto PV+ cells are synthesised locally at developing synapses. So, local translation contributes to brain wiring not only during axon guidance but also in the final stages of circuit assembly.

6/8 A fascinating finding is that many genes linked to #autism seem to be dysregulated at the synapses by the loss of ErbB4 in PV+ interneurons, suggesting that the synapses between excitatory pyramidal cells and PV+ cells are a hotspot for genetic risk factors in #ASD

7/8 In sum, local protein translation is regulated at the level of specific connections to control synapse formation in the nervous system. Funded by @IHIEurope @Aims2Trials @SFARIorg and brought to you by the amazing talent of @clembrnrd @DExpositoAlonso @MartijnSelten et al

8/8 Here’s a link to the paper @ScienceMagazine if you want to dig in science.org/doi/10.1126/sc… Thanks for sharing! @dev_neuro @MRC_CNDD @KingsIoPPN @Aims2Trials @SFARIorg