Erbb4 Deletion from Fast-Spiking Interneurons Causes Schizophrenia-like Phenotypes
Open accessAbstract
Genetic variation in neuregulin and its ErbB4 receptor has been linked to schizophrenia, although little is known about how they contribute to the disease process. Here, we have examined conditional Erbb4 mouse mutants to study how disruption of specific inhibitory circuits in the cerebral cortex may cause large-scale functional deficits. We found that deletion of ErbB4 from the two main classes of fast-spiking interneurons, chandelier and basket cells, causes relatively subtle but consistent synaptic defects. Surprisingly, these relatively small wiring abnormalities boost cortical excitability, increase oscillatory activity, and disrupt synchrony across cortical regions. These functional deficits are associated with increased locomotor activity, abnormal emotional responses, and impaired social behavior and cognitive function. Our results reinforce the view that dysfunction of cortical fast-spiking interneurons might be central to the pathophysiology of schizophrenia.
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Increased activity of pyramidal cells might be a consequence of abnormal interneuron function.
“Mechanistically, increased activity of pyramidal cells might be a consequence of abnormal interneuron function, as previously shown in a genetic mouse model for schizophrenia 68 ,”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [68]
Developmental disruption of PV+ fast spiking interneurons causes abnormal gamma oscillations and long-range synchrony defects between the hippocampus and the prefrontal cortex in animal models.
“In addition to a possible link with striatal hyperdopaminergia, studies in animal models have shown that developmental disruption of PV+ fast spiking interneurons causes other phenotypes that are characteristic of schizophrenia, including abnormal gamma oscillations and long-range synchrony defects between the hippocampus and the prefrontal cortex 68 .”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [68]
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- Authors
- del Pino, I., García-Frigola, C., Dehorter, N., Brotons-Mas, J. R., Alvarez-Salvado, E., Martínez de Lagrán, M., Ciceri, G., Gabaldón, M. V., Moratal, D., Dierssen, M., Canals, S., Marín, O., & Rico, B.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Centro de Biomateriales e Ingeniería Tisular (ES)
- Universitat Pompeu Fabra (ES)
- Corresponding author
- Rico, Beatriz
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 79
- Issue
- 6
- Pages
- 1152-1168
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2103905237
- Cited by
- 314
- References
- 12
- Citations by year
- 2026: 15 · 2025: 23 · 2024: 17 · 2023: 21 · 2022: 25 · 2021: 28 · 2020: 20 · 2019: 21 · 2018: 22 · 2017: 22 · 2016: 26 · 2015: 35 · 2014: 36 · 2013: 3
- FWCI
- 23.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- RiuNet (Universitat Politècnica de València) (submittedVersion, cc-by-nc-nd)
- Funders
- Eli Lilly and Company
- York University
- University College London
- University College Dublin
- Universität Zürich
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- ErbB4, neuregulin, schizophrenia, fast-spiking interneurons, chandelier cells, basket cells, conditional knockout mice, inhibitory circuits, cortical excitability, cortical oscillations, locomotor activity, emotional responses, social behavior, cognitive impairment, synaptic defects
- MeSH terms
- Action Potentials, Animals, Animals, Newborn, Brain, Cognition Disorders, Disease Models, Animal, Glutamate Decarboxylase, Interneurons, Male, Mice, Transgenic, Motor Activity, Mutation, Nerve Tissue Proteins, Synaptic Transmission, Parvalbumins, Phenotype, Proteins, Receptors, GABA-A, Schizophrenia, Social Behavior, Statistics as Topic, Transcription Factors, Electroporation, Patch-Clamp Techniques, Maze Learning, RNA, Untranslated, Green Fluorescent Proteins, Mice, LIM-Homeodomain Proteins, ErbB Receptors, Receptor, ErbB-4, In Vitro Techniques
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