Genetic labeling reveals novel cellular targets of schizophrenia susceptibility gene: distribution of GABA and non-GABA ErbB4-positive cells in adult mouse brain
Open accessAbstract
Neuregulin 1 (NRG1) and its receptor ErbB4 are schizophrenia risk genes. NRG1-ErbB4 signaling plays a critical role in neural development and regulates neurotransmission and synaptic plasticity. Nevertheless, its cellular targets remain controversial. ErbB4 was thought to express in excitatory neurons, although recent studies disputed this view. Using mice that express a fluorescent protein under the promoter of the ErbB4 gene, we determined in what cells ErbB4 is expressed and their identity. ErbB4 was widely expressed in the mouse brain, being highest in amygdala and cortex. Almost all ErbB4-positive cells were GABAergic in cortex, hippocampus, basal ganglia, and most of amygdala in neonatal and adult mice, suggesting GABAergic transmission as a major target of NRG1-ErbB4 signaling in these regions. Non-GABAergic, ErbB4-positive cells were present in thalamus, hypothalamus, midbrain, and hindbrain. In particular, ErbB4 is expressed in serotoninergic neurons of raphe nuclei but not in norepinephrinergic neurons of the locus ceruleus. In hypothalamus, ErbB4 is present in neurons that express oxytocin. Finally, ErbB4 is expressed in a group of cells in the subcortical areas that are positive for S100 calcium binding protein β. These results identify novel cellular targets of NRG1-ErbB4 signaling.
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ErbB4 is restricted to specific interneuron types in the adult cortex but is present in most cortical interneurons around birth.
“Although the expression of ErbB4 is confined to specific types of interneuron in the adult cortex (Fazzari et al., 2010; Neddens and Buonanno, 2010; Vullhorst et al., 2009), ErbB4 is expressed in the majority of cortical interneurons at perinatal stages (Bean et al., 2014).”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Bean et al., 2014
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Development and Functional Diversification of Cortical Interneurons
Lim, L., Mi, D., Llorca, A., & Marín, O. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.009 · Cited by 714 · see citing works
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- Authors
- Bean, J. C., Lin, T. W., Sathyamurthy, A., Liu, F., Yin, D.-M., Xiong, W.-C., & Mei, L.
- Affiliations
- Augusta University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2014-10-01
- Volume
- 34
- Issue
- 40
- Pages
- 13549-13566
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4180480
- OpenAlex
- W2092929635
- Cited by
- 105
- References
- 72
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 6 · 2023: 8 · 2022: 7 · 2021: 20 · 2020: 9 · 2019: 7 · 2018: 15 · 2017: 12 · 2016: 7 · 2015: 3 · 2014: 1
- FWCI
- 5.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Keywords
- ErbB4, neuregulin-1, schizophrenia risk genes, GABAergic neurons, serotonergic neurons, raphe nuclei, oxytocin neurons, hypothalamus, amygdala, S100β, adult mouse brain
- MeSH terms
- Age Factors, Animals, Animals, Newborn, Brain, Cells, Cultured, gamma-Aminobutyric Acid, Glutamate Decarboxylase, Luminescent Proteins, Mice, Transgenic, Nerve Tissue Proteins, Neurons, Green Fluorescent Proteins, Mice, Receptor, ErbB-4
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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