The Metabotropic Glutamate Receptor, mGluR5, is a Key Determinant of Good and Bad Spatial Learning Performance and Hippocampal Synaptic Plasticity
Abstract
Hippocampal synaptic plasticity is expressed to very different extents in distinct rat strains in vivo. This may correlate with differences in learning ability. We investigated whether the metabotropic glutamate receptor mGluR5 contributes to differences in long-term potentiation (LTP) and learning in freely moving hooded Lister (HL) and Wistar rats. High-frequency tetanization (HFT) generated robust CA1 LTP in Wistar rats (> 24 h) and incremental potentiation in HL rats. The mGluR5 antagonist 2-methyl-6-(phenylethynyl) pyridine (MPEP; 1.8 microg), applied intracerebrally, impaired LTP from approximately 60 min onwards in Wistar and from 24 h in HL rats. HFT generated LTP in the dentate gyrus (DG) of Wistar rats (> 24 h), which was blocked by MPEP, and MPEP-resistant short-term depression in HL rats. Training for 10 days in an eight-arm radial maze revealed no working memory differences, but better reference memory performance in Wistar compared with HL rats. Daily application of MPEP (1.8 microg) impaired working and reference memory in Wistar rats. In HL rats, working memory was impaired but reference memory was unaffected. Western blot analysis revealed lower expression of mGluR5 in HL compared with Wistar rats. MGluR1 expression was equivalent. These data reveal striking mGluR5-dependent differences in spatial learning in different rat strains, which correlate to synaptic plasticity and mGluR5 expression levels.
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Learning performance and response depend on the frequency of mGluR5 expression in the hippocampus.
“In this capacity, learning performance and response depend on the frequency of mGluR5 expression in the hippocampus [38,39].”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [39]
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Aiba, A. (1994) · Cell · doi:10.1016/0092-8674(94)90204-6 · Cited by 614 · see citing works
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- Naie K, Manahan-Vaughan D (2004b) Pharmacological antagonism of metabotropic glutamate receptor 1 (mGluR1) regulates LTP and spatial reference memory in the dentate gyrus of freely moving rats via NMDA and mGluR-dependent mechanisms. Eur J Neurosci (in press).
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Verpelli, C., Dvoretskova, E., Vicidomini, C., Rossi, F., Chiappalone, M., Schoen, M., Di Stefano, B., Mantegazza, R., Broccoli, V., Böckers, T. M., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.258384 · Cited by 197 · see citing works
Molecular and cellular aspects of age-related cognitive decline and Alzheimer’s disease
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Vecera, C. M., C. Courtes, A., Jones, G., Soares, J. C., & Machado-Vieira, R. (2023) · Pharmaceuticals · doi:10.3390/ph16111572 · Cited by 48 · see citing works
“In this capacity, learning performance and response depend on the frequency of mGluR 5 expression in the hippocampus [38,39].”
BackgroundMGlu5 antagonism impairs exploration and memory of spatial and non-spatial stimuli in rats
Christoffersen, G. R. J., Simonyi, A., Schachtman, T. R., Clausen, B., Clement, D., Bjerre, V. K., Mark, L. T., Reinholdt, M., Schmith-Rasmussen, K., & Zink, L. V. B. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.03.032 · Cited by 42 · see citing works
Impairments of exploration and memory after systemic or prelimbic D1-receptor antagonism in rats
Clausen, B., Schachtman, T. R., Mark, L. T., Reinholdt, M., & Christoffersen, G. R. J. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.03.069 · Cited by 41 · see citing works
Holmes, S. E., Asch, R. H., Davis, M. T., DellaGioia, N., Pashankar, N., Gallezot, J.-D., Nabulsi, N., Matuskey, D., Sanacora, G., Carson, R. E., et al. (2023) · Biological Psychiatry · doi:10.1016/j.biopsych.2022.10.018 · Cited by 27 · see citing works
- Authors
- Manahan-Vaughan, D., & Braunewell, K.-H.
- Affiliations
- Humboldt-Universität zu Berlin (DE)
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-02-09
- Volume
- 15
- Issue
- 11
- Pages
- 1703-1713
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- OpenAlex
- W2072397199
- Cited by
- 138
- References
- 1
- Citations by year
- 2024: 2 · 2023: 2 · 2022: 6 · 2021: 5 · 2020: 2 · 2019: 6 · 2018: 8 · 2017: 12 · 2016: 10 · 2015: 8 · 2014: 8 · 2013: 7 · 2012: 9
- FWCI
- 3.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- hippocampal synaptic plasticity, long-term potentiation, spatial learning, reference memory, working memory, Lister hooded rats, Wistar rats, rat strain differences, MPEP, CA1, dentate gyrus, short-term depression, mGluR1, glutamate receptor expression
- MeSH terms
- Animals, Discrimination Learning, Hippocampus, Male, Memory, Synaptic Transmission, Neuronal Plasticity, Psychomotor Performance, Space Perception, Species Specificity, Rats, Wistar, Long-Term Potentiation, Receptors, Metabotropic Glutamate, Maze Learning, Rats, Receptor, Metabotropic Glutamate 5
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