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Neuron. 2017 Aug 16;95(4):884-895.e9. doi: 10.1016/j.neuron.2017.07.034.

Developmental Dysfunction of VIP Interneurons Impairs Cortical Circuits.

Author information

1
Yale University School of Medicine, Department of Neuroscience, 333 Cedar St., New Haven, CT, 06520, USA; Kavli Institute of Neuroscience, Yale University, 333 Cedar St., New Haven CT, 06520, USA.
2
Yale University School of Medicine, Department of Neuroscience, 333 Cedar St., New Haven, CT, 06520, USA; Kavli Institute of Neuroscience, Yale University, 333 Cedar St., New Haven CT, 06520, USA; Ernst Strüngmann Institute (ESI) for Neuroscience in Cooperation with Max Planck Society, Deutschordenstraße 46, 60528 Frankfurt, Germany.
3
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
4
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; HHMI, Stanford University, Stanford, CA 94305, USA; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
5
Yale University School of Medicine, Department of Neuroscience, 333 Cedar St., New Haven, CT, 06520, USA; Kavli Institute of Neuroscience, Yale University, 333 Cedar St., New Haven CT, 06520, USA. Electronic address: jess.cardin@yale.edu.

Abstract

GABAergic interneurons play important roles in cortical circuit development. However, there are multiple populations of interneurons and their respective developmental contributions remain poorly explored. Neuregulin 1 (NRG1) and its interneuron-specific receptor ERBB4 are critical genes for interneuron maturation. Using a conditional ErbB4 deletion, we tested the role of vasoactive intestinal peptide (VIP)-expressing interneurons in the postnatal maturation of cortical circuits in vivo. ErbB4 removal from VIP interneurons during development leads to changes in their activity, along with severe dysregulation of cortical temporal organization and state dependence. These alterations emerge during adolescence, and mature animals in which VIP interneurons lack ErbB4 exhibit reduced cortical responses to sensory stimuli and impaired sensory learning. Our data support a key role for VIP interneurons in cortical circuit development and suggest a possible contribution to pathophysiology in neurodevelopmental disorders. These findings provide a new perspective on the role of GABAergic interneuron diversity in cortical development. VIDEO ABSTRACT.

KEYWORDS:

ErbB4; GABAergic; VIP; cholinergic; cortex; development; gCAMP6; interneuron; somatostatin; visual

PMID:
28817803
PMCID:
PMC5595250
[Available on 2018-08-16]
DOI:
10.1016/j.neuron.2017.07.034
[Indexed for MEDLINE]
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