Primary Cilia Signaling Shapes the Development of Interneuronal Connectivity

Publication date: 7 August 2017
Source:Developmental Cell, Volume 42, Issue 3
Author(s): Jiami Guo, James M. Otis, Holden Higginbotham, Chase Monckton, JrGang Cheng, Aravind Asokan, Kirk Mykytyn, Tamara Caspary, Garret D. Stuber, E.S. Anton
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.

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Teaser

Growth and connectivity of interneurons are fundamental to the formation of functional neural circuitry. Guo et al. show that primary cilia signaling, via Arl13b-GPCR pathway, promotes interneuronal connectivity and inhibitory circuit formation. Primary cilia signaling is a non-synaptic signaling mechanism through which environmental signals can shape and refine interneuronal networks.


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