Nova proteins direct synaptic integration of somatostatin interneurons through activity-dependent alternative splicing

Leena Ali Ibrahim*, Brie Wamsley, Norah Alghamdi, Nusrath Yusuf, Elaine Sevier, Ariel Hairston, Mia Sherer, Xavier Hubert Jaglin, Qing Xu, Lihua Guo, Alireza Khodadadi-Jamayran, Emilia Favuzzi, Yuan Yuan, Jordane Dimidschstein, Robert B. Darnell, Gordon Fishell*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Somatostatin interneurons are the earliest born population of cortical inhibitory cells. They are crucial to support normal brain development and function; however, the mechanisms underlying their integration into nascent cortical circuitry are not well understood. In this study, we begin by demonstrating that the maturation of somatostatin interneurons in mouse somatosensory cortex is activity dependent. We then investigated the relationship between activity, alternative splicing, and synapse formation within this population. Specifically, we discovered that the Nova family of RNA-binding proteins are activity-dependent and are essential for the maturation of soma-tostatin interneurons, as well as their afferent and efferent connectivity. Within this population, Nova2 preferentially mediates the alternative splicing of genes required for axonal formation and synaptic function independently from its effect on gene expression. Hence, our work demonstrates that the Nova family of proteins through alternative splicing are centrally involved in coupling developmental neuronal activity to cortical circuit formation.

Original languageEnglish (US)
Article numbere86842
JournaleLife
Volume12
DOIs
StatePublished - Jun 2023

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology

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