A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)3269-3280
Number of pages12
JournalCell Reports
Volume17
Issue number12
DOIs
Publication statusPublished - Dec 20 2016

Keywords

  • Journal Article

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    Ehrmann, I., Gazzara, M. R., Pagliarini, V., Dalgliesh, C., Kheirollahi-Chadegani, M., Xu, Y., Cesari, E., Danilenko, M., Maclennan, M., Lowdon, K., Vogel, T., Keskivali-Bond, P., Wells, S., Cater, H., Fort, P., Santibanez-Koref, M., Middei, S., Sette, C., Clowry, G. J., ... Elliott, D. J. (2016). A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior. Cell Reports, 17(12), 3269-3280. https://doi.org/10.1016/j.celrep.2016.12.002