Metabotropic glutamate receptor subtype 7 ablation causes deficit in fear response and conditioned taste aversion
Open accessAbstract
Metabotropic glutamate receptors (mGluRs) consist of eight different subtypes and exert their effects on second messengers and ion channels via G-proteins. The function of individual mGluR subtypes in the CNS, however, largely remains to be clarified. We examined the fear response of freezing after electric shock in wild-type and mGluR7(-/-) knockout littermates. Wild-type mice displayed freezing immediately after and 1 d after footshock. In comparison, mGluR7(-/-) knockout mice showed significantly reduced levels in both immediate postshock and delayed freezing responses. However, the knockout mice exhibited no abnormalities in pain sensitivity and locomotor activity. To further examine amygdala-dependent behavior, we performed conditioned taste aversion (CTA) experiments. In wild-type mice, the administration of saccharin followed by intraperitoneal injection of the malaise-inducing agent LiCl resulted in an association between saccharin and LiCl. This association caused strong CTA toward saccharin. In contrast, mGluR7(-/-) knockout mice failed to associate between the taste and the negative reinforcer in CTA experiments. Again, the knockout mice showed no abnormalities in taste preference and in the sensitivity to LiCl toxicity. These results indicate that mGluR7 deficiency causes an impairment of two distinct amygdala-dependent behavioral paradigms. Immunohistochemical and immunoelectron-microscopic analyses showed that mGluR7 is highly expressed in amygdala and preferentially localized at the presynaptic axon terminals of glutamatergic neurons. Together, these findings strongly suggest that mGluR7 is involved in neural processes subserving amygdala-dependent averse responses.
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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 et al., 1999
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- Authors
- Masugi, M., Yokoi, M., Shigemoto, R., Muguruma, K., Watanabe, Y., Sansig, G., van der Putten, H., & Nakanishi, S.
- Affiliations
- Department of Biological Sciences (RU)
- Kyoto University (JP)
- Novartis (Switzerland) (CH)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1999-02-01
- Volume
- 19
- Issue
- 3
- Pages
- 955-963
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6782134
- OpenAlex
- W1932328925
- Cited by
- 211
- References
- 66
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 7 · 2019: 8 · 2018: 4 · 2017: 6 · 2016: 6 · 2015: 9 · 2014: 3 · 2013: 8 · 2012: 13
- FWCI
- 5.42
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- mGluR7, fear response, freezing behavior, conditioned taste aversion, amygdala, G protein signaling, aversive learning, pain sensitivity, locomotor activity
- MeSH terms
- Animals, Avoidance Learning, Conditioning, Psychological, Fear, Taste, Presynaptic Terminals, Receptors, Metabotropic Glutamate, Mice, Knockout, Mice
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