Developmental Dysfunction of VIP Interneurons Impairs Cortical Circuits
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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.
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Cholinergic receptors are expressed by inhibitory and excitatory cortical neurons and on the terminals of thalamocortical neurons.
“Cholinergic receptors are expressed by inhibitory and excitatory cortical neurons119,124,158–164, as well as on the terminals of thalamocortical neurons165–169.”
From Mechanisms underlying gain modulation in the cortex (2020) · cites this paper as [124]
VIP+ interneurons are strongly depolarized by nicotine or ACh.
“In particular, VIP+ interneurons express nAChRs and are strongly depolarized by nicotine or ACh119,124,163.”
From Mechanisms underlying gain modulation in the cortex (2020) · cites this paper as [124]
VIP+ interneurons express nAChRs.
“In particular, VIP+ interneurons express nAChRs and are strongly depolarized by nicotine or ACh119,124,163.”
From Mechanisms underlying gain modulation in the cortex (2020) · cites this paper as [124]
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References 118 · Cited by 135
- Authors
- Batista-Brito, R., Vinck, M., Ferguson, K. A., Chang, J. T., Laubender, D., Lur, G., Mossner, J. M., Hernandez, V. G., Ramakrishnan, C., Deisseroth, K., Higley, M. J., & Cardin, J. A.
- Affiliations
- Max Planck Society (DE)
- Yale University (US)
- Stanford University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Cardin, Jessica A.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 95
- Issue
- 4
- Pages
- 884-895.e9
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC5595250
- OpenAlex
- W2524300278
- Cited by
- 135
- References
- 118
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 9 · 2023: 11 · 2022: 16 · 2021: 22 · 2020: 27 · 2019: 15 · 2018: 11 · 2017: 4
- FWCI
- 7.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Brown-Coxe fellowship
- Jane Coffin Childs Fellowship
- NARSAD Young Investigator Award (BR 2012-121)
- Rubicon fellowship
- Human Frontiers Postdoctoral Fellowship
- NIH (R01 MH099045, R01 MH102365, R01 EY022951)
- Smith Family Award for Excellence in Biomedical Research
- Klingenstein Fellowship Award
- Alfred P. Sloan Fellowship
- McKnight Fellowship to J.A.C
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- vasoactive intestinal peptide interneurons, ErbB4, neuregulin-1, GABAergic interneurons, cortical circuit development, interneuron maturation, conditional gene deletion, sensory learning, sensory responses, neurodevelopmental disorders, adolescence
- MeSH terms
- Action Potentials, Animals, Animals, Newborn, Calcium, Cerebral Cortex, Developmental Disabilities, Disease Models, Animal, Interneurons, Mice, Transgenic, Photic Stimulation, Somatostatin, Spectrum Analysis, Vasoactive Intestinal Peptide, Visual Pathways, Signal Detection, Psychological, Homeodomain Proteins, Patch-Clamp Techniques, Gene Expression Regulation, Developmental, Mice, Receptor, ErbB-4, In Vitro Techniques
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