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.
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., Barash, Y., Cunningham, M. O., Elliott, D. J., A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior, <<CELL REPORTS>>, 2016; 17 (12): 3269-3280. [doi:10.1016/j.celrep.2016.12.002] [http://hdl.handle.net/10807/124733]
A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior
Pagliarini, Vittoria;Cesari, Eleonora;Sette, Claudio;
2016
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.
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