A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior

作者：Ehrmann Ingrid; Gazzara Matthew R; Pagliarini Vittoria; Dalgliesh Caroline; Kheirollahi Chadegani Mahsa; Xu Yaobo; Cesari Eleonora; Danilenko Marina; Maclennan Marie; Lowdon Kate; Vogel Tanja; Keskivali Bond Piia; Wells Sara; Cater Heather; Fort Philippe; Santibanez Koref Mauro; Middei Silvia; Sette Claudio; Clowry Gavin J; Barash Yoseph; Cunningham Mark O; Elliott David J

来源：Cell Reports, 2016, 17(12): 3269-3280.

DOI：10.1016/j.celrep.2016.12.002

The brain is made up of trillions of synaptic connections that together form neural networks needed for normal brain function and behavior. SLM2 is a member of a conserved family of RNA binding proteins, including Sam68 and SLM1, that control splicing of Neurexin1-3 pre-mRNAs. Whether SLM2 affects neural network activity is unknown. Here, we find that SLM2 levels are maintained by a homeostatic feedback control pathway that predates the divergence of SLM2 and Sam68. SLM2 also controls the splicing of Tomosyn2, LysoPLD/ATX, Dgkb, Kif21a, and Cask, each of which are important for synapse function. Cortical neural network activity dependent on synaptic connections between SLM2-expressing-pyramidal neurons and interneurons is decreased in Slm2-null mice. Additionally, these mice are anxious and have a decreased ability to recognize novel objects. Our data reveal a pathway of SLM2 homeostatic auto-regulation controlling brain network activity and behavior.

• 出版日期2016-12-20
• 单位河北医科大学