Thread by @emiliafavuzzi

1. Our work showing that GABA-receptive microglia selectively sculpt inhibitory synapses during development is out @CellCellPress: authors.elsevier.com/c/1dMWhL7PXe~wk
Wonderful collaboration w/ @stevens1lab @Datta_Lab Farhi lab @RichBonneauNYU @harvardmed @broadinstitute thread⬇︎

2. Work from many labs has shown that #microglia are key regulators of synapse #development but we know that not all #synapses are created equal. The best example? Excitatory vs inhibitory synapses. Are microglia a jack of all trades or do they focus on specific synapse types?

3. At the outset, we were unsure whether microglia even regulate the development of inhibitory synapses. The answer to this was "they do”. When we depleted microglia during cortical development, we observed increases in both excitatory and inhibitory synapses

4. We also found that microglia directly interact with inhibitory synapses during development but not equally. Using in vivo 2p imaging, we discovered that some engage with GABAergic inhibitory synapses while other microglia almost ignore them.

5. Intriguingly, a subset of microglia express GABAb receptors. We found that these GABA-receptive microglia preferentially contact inhibitory synapses.

6. When we remove GABAbRs from microglia, we see a synapse-specific effect! The loss of GABAbRs on microglia increases the number of inhibitory synapses but has no effect on excitatory synapses.

7. #scRNAseq showed that removing microglial GABAbRs alters the expression of genes involved in synapse remodeling. Are these genes only changed in GABA-receptive microglia? Expression of GABAbRs in microglia was too low to answer this question with scRNAseq so we used #MERFISH.

8. MERFISH allowed us to “identify” GABAbR-expressing microglia and showed that the transcriptional changes resulting from GABAbRs removal are indeed restricted to GABA-receptive microglia.

9. Does removing GABAbRs from microglia lead to behavioral changes? It does. Using #MoSeq we found that mice lacking GABAbRs on their microglia are hyperactive.

10. This work would not have been possible if it wasn’t for an amazing team of dedicated collaborators, including @Su_hang_ @gs512 twitterless L Binan @LeenaAIbrahim @marianf_otero Thanks to @EMBO for their support and thanks for sharing!