Department of Neurobiology, Harvard Medical School, Boston, United States; Biological and Environmental Sciences and Engineering Division (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia; Stanley Center at the Broad, Cambridge, United States
Brie Wamsley
NYU Neuroscience Institute and the Department of Neuroscience and Physiology, Smilow Research Center, New York University School of Medicine, New York, United States
Norah Alghamdi
Biological and Environmental Sciences and Engineering Division (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia
Nusrath Yusuf
Department of Neurobiology, Harvard Medical School, Boston, United States; Stanley Center at the Broad, Cambridge, United States; NYU Neuroscience Institute and the Department of Neuroscience and Physiology, Smilow Research Center, New York University School of Medicine, New York, United States
Elaine Sevier
Department of Neurobiology, Harvard Medical School, Boston, United States; Stanley Center at the Broad, Cambridge, United States
Ariel Hairston
Department of Neurobiology, Harvard Medical School, Boston, United States
Mia Sherer
Department of Neurobiology, Harvard Medical School, Boston, United States; Stanley Center at the Broad, Cambridge, United States
Xavier Hubert Jaglin
NYU Neuroscience Institute and the Department of Neuroscience and Physiology, Smilow Research Center, New York University School of Medicine, New York, United States
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 somatostatin 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.
