Amygdala NRG1–ErbB4 Is Critical for the Modulation of Anxiety-Like Behaviors
Open accessAbstract
Anxiety disorder is related to the pathophysiology of psychiatric diseases, including major depression, substance abuse, and schizophrenia. The amygdala is important for manifestation and modulation of anxiety. However, relatively little is known regarding the mechanisms that control the amygdala inhibitory activity that is involved in anxiety. We found that almost all ErbB4, which is the only autonomous receptor of neuregulin 1 (NRG1) in the basolateral amygdala (BLA), was expressed in GABAergic neurons. Endogenous NRG1-ErbB4 signaling pathway in the BLA could modulate anxiety-like behaviors and GABA release, whereas it had no effect on glutamatergic transmission. The administration of NRG1 into the BLA of high-anxiety mice alleviated their anxiety and enhanced GABAergic neurotransmission. Moreover, exogenous NRG1 also produced an anxiolytic effect in the stressed mice. Together, these observations indicated that NRG1-ErbB4 signaling is critical to maintaining GABAergic activity in the amygdala and thus to modulating anxiety-like behaviors. Because NRG1 and ErbB4 are susceptibility genes of schizophrenia, our findings might also help to explain the potential mechanism of emotional abnormality in schizophrenia.
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ErbB4, the receptor for NRG1 on GABAergic neurons, has been proposed as a possible drug target for depression, anxiety, and schizophrenia.
“The Neuregulin 1 (NRG1) receptor ErbB4, found on GABAergic neurones, has been identified as a potentially druggable target for depression, anxiety and schizophrenia 45.”
From Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions (2019) · cites this paper as [45]
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- Authors
- Bi, L.-L., Sun, X.-D., Zhang, J., Lu, Y.-S., Chen, Y.-H., Wang, J., Geng, F., Liu, F., Zhang, M., Liu, J.-H., Li, X.-W., Mei, L., & Gao, T.-M.
- Affiliations
- Augusta University (US)
- Southern Medical University (CN)
- Corresponding author
- Mei, Lin
- Gao, Tian-Ming
- Venue
- Neuropsychopharmacology
- Published
- 2014-10-13
- Volume
- 40
- Issue
- 4
- Pages
- 974-986
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC4330511
- OpenAlex
- W1970662525
- Cited by
- 76
- References
- 52
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 4 · 2023: 5 · 2022: 10 · 2021: 5 · 2020: 7 · 2019: 6 · 2018: 13 · 2017: 8 · 2016: 7 · 2015: 1
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31430032, 81329003, U1201225)
- National Institutes of Health
- Program for Changjiang Scholars and Innovative Research Team in University (IRT1142)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- neuregulin-1, ErbB4, amygdala, basolateral amygdala, anxiety-like behavior, GABAergic neurons, GABA release, anxiolytic effects, stress, schizophrenia, susceptibility genes
- MeSH terms
- Nogo Receptor 1, Amygdala, Animals, Anxiety, Disease Models, Animal, Enzyme Inhibitors, Exploratory Behavior, Feeding Behavior, gamma-Aminobutyric Acid, Gene Expression Regulation, Glutamate Decarboxylase, Male, Mice, Inbred C57BL, Mice, Transgenic, Myelin Proteins, Pyrimidines, Quinazolines, Reaction Time, Receptors, Cell Surface, Signal Transduction, Maze Learning, Tyrphostins, Mice, GPI-Linked Proteins, Receptor, ErbB-4, In Vitro Techniques
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