An alternative splicing switch shapes neurexin repertoires in principal neurons versus interneurons in the mouse hippocampus
- University of Basel, Switzerland
Abstract
The unique anatomical and functional features of principal and interneuron populations are critical for the appropriate function of neuronal circuits. Cell type-specific properties are encoded by selective gene expression programs that shape molecular repertoires and synaptic protein complexes. However, the nature of such programs, particularly for post-transcriptional regulation at the level of alternative splicing is only beginning to emerge. We here demonstrate that transcripts encoding the synaptic adhesion molecules neurexin-1,2,3 are commonly expressed in principal cells and interneurons of the mouse hippocampus but undergo highly differential, cell type-specific alternative splicing. Principal cell-specific neurexin splice isoforms depend on the RNA-binding protein Slm2. By contrast, most parvalbumin-positive (PV+) interneurons lack Slm2, express a different neurexin splice isoform and co-express the corresponding splice isoform-specific neurexin ligand Cbln4. Conditional ablation of Nrxn alternative splice insertions selectively in PV+ cells results in elevated hippocampal network activity and impairment in a learning task. Thus, PV-cell-specific alternative splicing of neurexins is critical for neuronal circuit function
Article and author information
Author details
Funding
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Peter Scheiffele
European Research Council (SPLICECODE)
- Peter Scheiffele
National Competence Centre for Research NCCR_SYNAPA
- Peter Scheiffele
Innovative Medicines Initiatives, EU-AIMS
- Peter Scheiffele
Boehringer Ingelheim Fonds
- Lisa Traunmüller
Marie-Curie Mobility Fellowship European Union
- Dietmar Schreiner
Werner Siemens/Opportunities in Excellence Fellowship
- Thi-Minh Nguyen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Sacha B Nelson, Brandeis University, United States
Ethics
Animal experimentation: All animal procedures were reviewed and approved by the Kantonales Veterinäramt Basel-Stadt (Licence 2272). The Procedures were performed in strict accordance to the guidelines and every effort was mode to minimize suffering of the animals and to minimize animal numbers (either by replacement or optimization of procedures).
Version history
- Received: October 28, 2016
- Accepted: December 7, 2016
- Accepted Manuscript published: December 13, 2016 (version 1)
- Accepted Manuscript updated: December 14, 2016 (version 2)
- Version of Record published: January 5, 2017 (version 3)
- Version of Record updated: April 25, 2017 (version 4)
Copyright
© 2016, Nguyen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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An alternative splicing switch shapes neurexin repertoires in principal neurons versus interneurons in the mouse hippocampus
eLife 5:e22757.
https://doi.org/10.7554/eLife.22757
Further reading
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