title: An alternative splicing switch shapes neurexin repertoires in principal neurons versus interneurons in the mouse hippocampus.
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 ofNrxnalternative 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.
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Thi-Minh
authors.initials: TM
authors.lastname: Nguyen
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schreiner
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Le
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Lisa
authors.initials: L
authors.lastname: Traunmüller
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bornmann
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Peter
authors.identifier: 0000-0002-9516-9399
authors.initials: P
authors.lastname: Scheiffele
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002135:Calcium-Binding Proteins; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000502:physiology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000502:physiology*; D011498:Protein Precursors / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; C486528:Khdrbs3 protein, mouse; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; C527193:Nrxn1 protein, mouse; D011498:Protein Precursors; D016601:RNA-Binding Proteins; C542343:cerebellin 4 precursor, mouse; C583456:neurexin 3, mouse; C093175:neurexin II
keywords: GABA; activity; alternative splicing; cell biology; memory; mouse; neuroscience; synaptic specificity; synaptogenesis