Résumé
The brain is made up of trillions of synaptic connec-tions that together form neural networks needed fornormal brain function and behavior. SLM2 is a mem-ber of a conserved family of RNA binding proteins,including Sam68 and SLM1, that control splicing ofNeurexin1-3pre-mRNAs. Whether SLM2 affects neu-ral network activity is unknown. Here, we find thatSLM2 levels are maintained by a homeostatic feed-back control pathway that predates the divergenceof SLM2 and Sam68. SLM2 also controls the splicingofTomosyn2, LysoPLD/ATX, Dgkb, Kif21a,andCask, each of which are important for synapse func-tion. Cortical neural network activity dependent onsynaptic connections between SLM2-expressing-pyramidal neurons and interneurons is decreased inSlm2-null mice. Additionally, these mice are anxiousand have a decreased ability to recognize novelobjects. Our data reveal a pathway of SLM2 homeo-static auto-regulation controlling brain network ac-tivity and behavior.