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Free keywords:
Action Potentials/physiology
Animals
Animals, Newborn
Calcium/metabolism
Cerebral Cortex/*pathology
Developmental Disabilities/*genetics/*pathology
Disease Models, Animal
Gene Expression Regulation, Developmental/*genetics
Homeodomain Proteins/genetics/metabolism
In Vitro Techniques
Interneurons/metabolism/*pathology
Mice
Mice, Transgenic
Patch-Clamp Techniques
Photic Stimulation
Receptor, ErbB-4/genetics/metabolism
Signal Detection, Psychological/physiology
Somatostatin/genetics/metabolism
Spectrum Analysis
Vasoactive Intestinal Peptide/genetics/*metabolism
Visual Pathways/growth & development/pathology
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.
