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Increased amygdalar metabotropic glutamate receptor 7 mRNA in a genetic mouse model of impaired fear extinction

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Abstract

Rationale

Post-traumatic stress disorder (PTSD) is a devastating anxiety-related disorder which develops subsequent to a severe psychologically traumatic event. Only ~ 9% of people who experience such a trauma develop PTSD. It is clear that a number of factors, including genetics, influence whether an individual will develop PTSD subsequent to a trauma. The 129S1/SvImJ (S1) inbred mouse strain displays poor fear extinction and may be useful to model this specific aspect of PTSD. The metabotropic glutamate receptor 7 (mGlu7 receptor) has previously been shown to be involved in cognitive processes and anxiety-like behaviour placing it in a key position to regulate fear extinction processes. We sought to compare mGlu7 receptor mRNA levels in the S1 strain with those in the robustly extinguishing C57BL/6J (B6) inbred strain using in situ hybridisation (ISH) in three brain regions associated with fear extinction: the amygdala, hippocampus and prefrontal cortex (PFC).

Results

Compared to the B6 strain, S1 mice had increased mGlu7 receptor mRNA levels in the lateral amygdala (LA) and basolateral amygdala (BLA) subdivisions. An increase was also seen in the hippocampal CA1 and CA3 subregions of S1 mice. No difference in mGlu7 receptor levels were seen in the central nucleus (CeA) of the amygdala, dentate gyrus (DG) of the hippocampus or prefrontal cortex.

Conclusions

These data show altered mGlu7 receptor expression in key brain regions associated with fear extinction in two different inbred mouse strains which differ markedly in their fear extinction behaviour. Altered mGlu7 receptor levels may contribute to the deficit fear extinction processes seen in fear extinction in the S1 strain.

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Funding

JFC is supported by Science Foundation Ireland (SFI) (Grant Numbers 07/CE/BI368 and 12/RC/2273); the Irish Health Research Board. RMOC was supported by a postgraduate scholarship awarded by the Irish Research Council for Science Engineering and Technology (IRCSET). AH is supported by the NIAAA IRP. NS is supported by the Austrian Science Fund FWF SFB F4410.

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Author notes

  1. Richard M. O’Connor

    Present address: Department of Neuroscience, Icahn School of Medicine, Mount Sinai Hospital, New York, NY, USA

  2. Cian P. McCafferty

    Present address: Department of Neurology, Yale University School of Medicine, New Haven, CT, USA

Authors and Affiliations

  1. Department of Anatomy and Neuroscience and APC Microbiome Institute, University College Cork, Cork, Ireland

    Richard M. O’Connor, Cian P. McCafferty & John F. Cryan

  2. Department of Neuroscience, Icahn School of Medicine at Mount Sinai, S10-20 Hess CSM, 1470 Madison Avenue, New York, NY, 10029, USA

    Richard M. O’Connor

  3. Grupo de NeuroGastroBioquímica, Laboratorio e Química Biológica & Bioquímica de Sistemas, Instituto de Química, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile

    Javier A. Bravo

  4. Department of Pharmacology and Toxicology, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innsbruck, Austria

    Nicolas Singewald

  5. Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, USA

    Andrew Holmes

Authors
  1. Richard M. O’Connor
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  2. Cian P. McCafferty
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  3. Javier A. Bravo
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  4. Nicolas Singewald
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Corresponding author

Correspondence to Richard M. O’Connor.

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All experiments were conducted in accordance with the European Directive 86/609/EEC and the local Animal Care and Use Committees.

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The authors declare that they have no conflict of interest.

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This article belongs to a Special Issue on Psychopharmacology of Extinction.

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O’Connor, R.M., McCafferty, C.P., Bravo, J.A. et al. Increased amygdalar metabotropic glutamate receptor 7 mRNA in a genetic mouse model of impaired fear extinction. Psychopharmacology 236, 265–272 (2019). https://doi.org/10.1007/s00213-018-5031-4

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  • DOI: https://doi.org/10.1007/s00213-018-5031-4

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