| First Author | Nguyen TM | Year | 2016 |
| Journal | Elife | Volume | 5 |
| PubMed ID | 27960072 | Mgi Jnum | J:239448 |
| Mgi Id | MGI:5828938 | Doi | 10.7554/eLife.22757 |
| Citation | Nguyen TM, et al. (2016) An alternative splicing switch shapes neurexin repertoires in principal neurons versus interneurons in the mouse hippocampus. Elife 5:e22757 |
| abstractText | 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. |
