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Dev Cell. 2017 Aug 7;42(3):286-300.e4. doi: 10.1016/j.devcel.2017.07.010.

Primary Cilia Signaling Shapes the Development of Interneuronal Connectivity.

Author information

1
UNC Neuroscience Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
2
UNC Neuroscience Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
3
UNC Neuroscience Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
4
Department of Genetics and Gene Therapy Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
5
Department of Biological Chemistry and Pharmacology, Neuroscience Research Institute, The Ohio State University, Columbus, OH 43210, USA.
6
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
7
UNC Neuroscience Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
8
UNC Neuroscience Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. Electronic address: anton@med.unc.edu.

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.

KEYWORDS:

Arl13b; GPCR signaling; Joubert syndrome related disorders; autism spectrum disorders; ciliopathies; circuitry; interneurons; primary cilia

PMID:
28787594
PMCID:
PMC5571900
DOI:
10.1016/j.devcel.2017.07.010
[Indexed for MEDLINE]
Free PMC Article

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