Metabotropic glutamate receptor subtype 7 in the bed nucleus of the stria terminalis is essential for intermale aggression
Open accessAbstract
Metabotropic glutamate receptor subtype 7 (mGluR7) is a member of group III mGluRs, which localize to the presynaptic active zones of the mammalian central nervous system. Although histological, genetic, and electrophysiological studies ensure the importance of mGluR7, its roles in behavior and physiology remain largely unknown. Using a resident-intruder paradigm, we found a severe reduction in intermale aggressive behavior in mGluR7 knockout (KO) mice. We also found alterations in other social behaviors in male mGluR7 KO mice, including sexual behavior toward male intruders. Because olfaction is critical for rodent social behavior, including aggression, we performed an olfaction test, finding that mGluR7 KO mice failed to show interest in the smell of male urine. To clarify the olfactory deficit, we then exposed mice to urine and analyzed c-Fos-immunoreactivity, discovering a remarkable reduction in neural activity in the bed nucleus of the stria terminalis (BNST) of mGluR7 KO mice. Finally, intra-BNST administration of the mGluR7-selective antagonist 6-(4-methoxyphenyl)-5-methyl-3-pyridin-4-ylisoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP) also reproduced the phenotype of mGluR7 KO mice, including reduced aggression and altered social interaction. Thus mGluR7 may work as an 'enhancer of neural activity' in the BNST and is important for intermale aggression. Our findings demonstrate that mGluR7 is essential for social behavior and innate behavior. Our study on mGluR7 in the BNST will shed light on future therapies for emotional disorders in humans.
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Ablation of GRM7 can make mice less fearful and less aggressive.
“In another contrast with GRM2 and the Group II subfamily as a whole, ablation of GRM7 can make mice less fearful and less aggressive (Duvoisin et al., 2011;Masugi et al., 1999;Masugi-Tokita et al., 2016) correlating with a severe reduction in neuronal activity in the BNST.”
From Glutamate receptors in domestication and modern human evolution (2020) · cites this paper as Masugi-Tokita et al., 2016
Activation of the GRM7 subunit serves to enhance overall excitability of BNST neurons projecting to the PVN (and thus the stress response), perhaps through downregulation of glutamate release innervating GABAergic inhibitory interneurons.
“This suggests that activation of the GRM7 (mGluR7) subunit serves to enhance overall excitability of BNST neurons projecting to the PVN (and thus the stress response), perhaps through downregulation of glutamate release innervating GABAergic inhibitory interneurons (Masugi-Tokita et al., 2016).”
From Glutamate receptors in domestication and modern human evolution (2020) · cites this paper as Masugi-Tokita et al., 2016
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- Authors
- Masugi-Tokita, M., Flor, P. J., & Kawata, M.
- Affiliations
- Kyoto University (JP)
- University of Regensburg (DE)
- Kyoto Prefectural University of Medicine (JP)
- Corresponding author
- Masugi-Tokita, Miwako
- Venue
- Neuropsychopharmacology
- Published
- 2015-07-07
- Volume
- 41
- Issue
- 3
- Pages
- 726-735
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC4707819
- OpenAlex
- W1549109483
- Cited by
- 35
- References
- 58
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 9 · 2019: 6 · 2018: 4 · 2017: 2 · 2016: 1 · 2015: 1
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (729/2, FL729/2‐1)
- Ministry of Education, Culture, Sports, Science and Technology (24300128)
- Novartis Institutes for BioMedical Research
- Japan Society for the Promotion of Science (20500313, 24300128, 23500415, 20240036)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- mGluR7, bed nucleus of the stria terminalis, male-male aggression, resident-intruder paradigm, social behavior, sexual behavior, olfaction, innate behavior, emotional disorders
- MeSH terms
- Aggression, Amygdala, Animals, Exploratory Behavior, Male, Mice, Inbred C57BL, Neuropsychological Tests, Physical Stimulation, Pyridones, Septal Nuclei, Urine, Proto-Oncogene Proteins c-fos, Receptors, Metabotropic Glutamate, Mice, Knockout, Excitatory Amino Acid Antagonists, Olfactory Perception
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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