Developmental Dysfunction of VIP Interneurons Impairs Cortical Circuits

Renata Batista-Brito; Martin Vinck; Katie A. Ferguson; Jeremy T. Chang; David Laubender; Gyorgy Lur; James M. Mossner; Victoria G. Hernandez; Charu Ramakrishnan; Karl Deisseroth; Michael J. Higley; Jessica A. Cardin

doi:10.1016/j.neuron.2017.07.034

Developmental Dysfunction of VIP Interneurons Impairs Cortical Circuits

Renata Batista-Brito, Martin Vinck, Katie A. Ferguson, Jeremy T. Chang, David Laubender, Gyorgy Lur, James M. Mossner, Victoria G. Hernandez, Charu Ramakrishnan, Karl Deisseroth, Michael J. Higley, Jessica A. Cardin

Research output: Contribution to journal › Article › peer-review

89 Scopus citations

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.

Original language	English (US)
Pages (from-to)	884-895.e9
Journal	Neuron
Volume	95
Issue number	4
DOIs	https://doi.org/10.1016/j.neuron.2017.07.034
State	Published - Aug 16 2017
Externally published	Yes

Keywords

ErbB4
GABAergic
VIP
cholinergic
cortex
development
gCAMP6
interneuron
somatostatin
visual

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neuron.2017.07.034

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title = "Developmental Dysfunction of VIP Interneurons Impairs Cortical Circuits",

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.",

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author = "Renata Batista-Brito and Martin Vinck and Ferguson, {Katie A.} and Chang, {Jeremy T.} and David Laubender and Gyorgy Lur and Mossner, {James M.} and Hernandez, {Victoria G.} and Charu Ramakrishnan and Karl Deisseroth and Higley, {Michael J.} and Cardin, {Jessica A.}",

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AU - Batista-Brito, Renata

AU - Vinck, Martin

AU - Ferguson, Katie A.

AU - Chang, Jeremy T.

AU - Laubender, David

AU - Lur, Gyorgy

AU - Mossner, James M.

AU - Hernandez, Victoria G.

AU - Ramakrishnan, Charu

AU - Deisseroth, Karl

AU - Higley, Michael J.

AU - Cardin, Jessica A.

PY - 2017/8/16

Y1 - 2017/8/16

N2 - 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.

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Developmental Dysfunction of VIP Interneurons Impairs Cortical Circuits

Abstract

Keywords

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