Primary Cilia Signaling Shapes the Development of Interneuronal Connectivity

• Type of Material: Article
• Authors: Jiami Guo, University of North Carolina; James M. Otis, University of North Carolina; Holden Higginbotham, University of North Carolina; Chase Monckton, University of North Carolina; Gang Cheng, Jr, University of North Carolina; Aravind Asokan, University of North Carolina; Kirk Mykytyn, Ohio State University; Tamara Caspary, Emory University; Garret D. Stuber, University of North Carolina; E. S. Anton, University of North Carolina
• Language: English
• Date: 2017-08-07
• Publisher: Elsevier (Cell Press)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.devcel.2017.07.010
• Title of Journal or Parent Work: Developmental Cell
• ISSN: 1534-5807
• Volume: 42
• Issue: 3
• Start Page: 286
• End Page: +
• Grant/Funding Information: This research was supported by NIH grants NS 090029 and MH060929 to E.S.A and by the confocal imaging core of an NINDS institutional center core grant (5P30NS045892).; The Hepatorenal Fibrocystic Disease Core Center, UAB [DK074038]
• Keywords: ARL13B; NEURONAL CILIA; PROTEIN-COUPLED-RECEPTORS; Life Sciences & Biomedicine; JOUBERT-SYNDROME; DEVELOPING CEREBRAL-CORTEX; Developmental Biology; MECHANISMS; CAENORHABDITIS-ELEGANS; Science & Technology; Cell Biology; CORTICAL INTERNEURONS; BRAIN; VISUAL-CORTEX
• Research Categories: Biology, Neuroscience; Biology, Genetics; Biology, Cell

Abstract

Appropriate growth and synaptic integration of GABAergic inhibitory interneurons are essential for functional neural circuits in the brain. Here, we demonstrate that disruption of primary cilia function following the selective loss of ciliary GTPase Arl13b in interneurons impairs interneuronal morphology and synaptic connectivity, leading to altered excitatory/inhibitory activity balance. The altered morphology and connectivity of cilia mutant interneurons and the functional deficits are rescued by either chemogenetic activation of ciliary G-protein-coupled receptor (GPCR) signaling or the selective induction of Sstr3, a ciliary GPCR, in Arl13b-deficient cilia. Our results thus define a specific requirement for primary cilia-mediated GPCR signaling in interneuronal connectivity and inhibitory circuit formation.