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A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior

Lookup NU author(s): Dr Ingrid Ehrmann, Caroline Dalgliesh, Dr Yaobo Xu, Dr Marina Danilenko, Marie Maclennan, Dr Gavin Clowry, Professor Mark Cunningham, Professor David Elliott

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

The brain is made up of trillions of synaptic connections that together form neural networks needed fornormal 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 neuralnetwork activity is unknown. Here, we find thatSLM2 levels are maintained by a homeostatic feedbackcontrol pathway that predates the divergenceof SLM2 and Sam68. SLM2 also controls the splicingof Tomosyn2, LysoPLD/ATX, Dgkb, Kif21a, andCask, each of which are important for synapse function.Cortical neural network activity dependent onsynaptic connections between SLM2-expressingpyramidalneurons 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 homeostaticauto-regulation controlling brain network activityand behaviour.


Publication metadata

Author(s): Ehrmann I, Gazzara MR, 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, Sanibanez-Koref M, Middei S, Sette C, Clowry GJ, Barash Y, Cunningham MO, Elliott DJ

Publication type: Article

Publication status: Published

Journal: Cell Reports

Year: 2016

Volume: 17

Issue: 12

Pages: 3269-3280

Online publication date: 20/12/2016

Acceptance date: 29/11/2016

ISSN (electronic): 2211-1247

Publisher: Elsevier Inc

URL: http://dx.doi.org/10.1016/j.celrep.2016.12.002

DOI: 10.1016/j.celrep.2016.12.002


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