A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior

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

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

8 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)3269-3280
Numero di pagine12
RivistaCell Reports
Volume17
DOI
Stato di pubblicazionePubblicato - 2016

Keywords

  • Adaptor Proteins, Signal Transducing
  • Alternative Splicing
  • Animals
  • Behavior, Animal
  • Biochemistry, Genetics and Molecular Biology (all)
  • Homeostasis
  • Mice
  • Mice, Knockout
  • Nerve Net
  • Neural Cell Adhesion Molecules
  • Neurexin splicing
  • Pyramidal Cells
  • RNA Precursors
  • RNA binding proteins
  • RNA-Binding Proteins
  • RNA-seq
  • Synapses
  • alternative splicing
  • brain
  • gene expression
  • hippocampus
  • neuron
  • transcriptome

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