The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Conserved hippocampal cellular pathophysiology but distinct behavioural deficits in a new rat model of FXS
Open accessAbstract
Recent advances in techniques for manipulating genomes have allowed the generation of transgenic animals other than mice. These new models enable cross-mammalian comparison of neurological disease from core cellular pathophysiology to circuit and behavioural endophenotypes. Moreover they will enable us to directly test whether common cellular dysfunction or behavioural outcomes of a genetic mutation are more conserved across species. Using a new rat model of Fragile X Syndrome, we report that Fmr1 knockout (KO) rats exhibit elevated basal protein synthesis and an increase in mGluR-dependent long-term depression in CA1 of the hippocampus that is independent of new protein synthesis. These defects in plasticity are accompanied by an increase in dendritic spine density selectively in apical dendrites and subtle changes in dendritic spine morphology of CA1 pyramidal neurons. Behaviourally, Fmr1 KO rats show deficits in hippocampal-dependent, but not hippocampal-independent, forms of associative recognition memory indicating that the loss of fragile X mental retardation protein (FMRP) causes defects in episodic-like memory. In contrast to previous reports from mice, Fmr1 KO rats show no deficits in spatial reference memory reversal learning. One-trial spatial learning in a delayed matching to place water maze task was also not affected by the loss of FMRP in rats. This is the first evidence for conservation across mammalian species of cellular and physiological hippocampal phenotypes associated with the loss of FMRP. Furthermore, while key cellular phenotypes are conserved they manifest in distinct behavioural dysfunction. Finally, our data reveal novel information about the selective role of FMRP in hippocampus-dependent associative memory.
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“Such deletion is sufficient to cause FXS-like traits, such as deficits in sustained visuospatial attention [34], altered patterns of social interaction, and cognitive impairment [28], together with abnormal synaptic plasticity [32,35,36].”
From Brain Cholesterol Biosynthetic Pathway Is Altered in a Preclinical Model of Fragile X Syndrome (2022) · cites this paper as [35]
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Cites
Genome sequence of the Brown Norway rat yields insights into mammalian evolution
Gibbs, R. A., Weinstock, G. M., Metzker, M. L., Muzny, D. M., Sodergren, E. J., Scherer, S. E., Scott, G., Steffen, D. L., Worley, K. C., Burch, P. E., et al. (2004) · Nature · doi:10.1038/nature02426 · Cited by 2,170
Self-citationAltered synaptic plasticity in a mouse model of fragile X mental retardation
Huber, K. M., Gallagher, S. M., Warren, S. T., & Bear, M. F. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.122205699 · Cited by 1,349
Self-citationCorrection of Fragile X Syndrome in Mice
Dölen, G., Osterweil, E., Rao, B. S. S., Smith, G. B., Auerbach, B. D., Chattarji, S., & Bear, M. F. (2007) · Neuron · doi:10.1016/j.neuron.2007.12.001 · Cited by 979
Self-citationEvidence that fragile X mental retardation protein is a negative regulator of translation
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The translation of translational control by FMRP: therapeutic targets for FXS
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Chronic Pharmacological mGlu5 Inhibition Corrects Fragile X in Adult Mice
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Self-citationThe fragile X mental retardation protein inhibits translation via interacting with mRNA
Li, Z. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.11.2276 · Cited by 448
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Self-citationBhattacharya, A., Kaphzan, H., Alvarez-Dieppa, A. C., Murphy, J. P., Pierre, P., & Klann, E. (2012) · Neuron · doi:10.1016/j.neuron.2012.07.022 · Cited by 316
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Additional file 1 of Fmr1 exon 14 skipping in late embryonic development of the rat forebrain
Corrêa-Velloso, J. C., Linardi, A., Glaser, T., Velloso, F. J., Rivas, M. P., Leite, R. E. P., Grinberg, L. T., Ulrich, H., Akins, M. R., Chiavegatto, S., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19947736
Asiminas, A., Booker, S. A., Dando, O., Kozić, Z., Arkell, D., Inkpen, F. H., Sumera, A., Akyel, I., Kind, P. C., & Wood, E. R. (2024) · Figshare · doi:10.6084/m9.figshare.26555963
Self-citationAsiminas, A., Booker, S. A., Dando, O., Kozić, Z., Arkell, D., Inkpen, F. H., Sumera, A., Akyel, I., Kind, P. C., & Wood, E. R. (2024) · Figshare · doi:10.6084/m9.figshare.26555960
Self-citationREVIEW: HYPERACUSIS, ANIMAL MODELS, CHRONIC STRESS, AND AUTISM IN FRAGILE X
Salvi, R., Chen, Y.-C., & Auerbach, B. D. (2025) · Journal of Hearing Science · doi:10.17430/jhs/204553
Pathophysiological consequences of a Fragile X missense mutation
Garcia, M. P. (2020) · theses.fr (ABES) · doi:10.70675/b8e86263z5926z4a83zbaf6z0f61bf2d15f9
Rôle de la phosphodiestérase 2A dans la physiopathologie du syndrome de l’X fragile
Delhaye, S. (2021) · theses.fr (ABES) · doi:10.70675/e0fac395z63d4z46a4z944aza4037215ca98
Shukla, A., Rivera, E. L., Bladon, J. H., & Jadhav, S. P. (2026) · Journal of Neuroscience · doi:10.1523/jneurosci.0143-26.2026
Maio, B., Singh, A., Hector, R., Gadalla, K. K. E., Selfridge, J., Aria, F., Louros, S. R., Cobb, S., & Osterweil, E. K. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.12.731901
Self-citationVadher, A., Duszkiewicz, A. J., Wood, E. R., & Dudchenko, P. A. (2026) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2026.1929983
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Metadata
- Authors
- Till, S. M., Asiminas, A., Jackson, A. D., Katsanevaki, D., Barnes, S. A., Osterweil, E. K., Bear, M. F., Chattarji, S., Wood, E. R., Wyllie, D. J. A., & Kind, P. C.
- Affiliations
- University of Edinburgh (GB)
- Institute for Stem Cell Biology and Regenerative Medicine (IN)
- Howard Hughes Medical Institute (US)
- Tata Institute of Fundamental Research (IN)
- Corresponding author
- Kind, Peter C.
- ORCID
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-08-04
- Volume
- 24
- Issue
- 21
- Pages
- 5977-5984
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- PMC
- PMC4599667
- OpenAlex
- W1893201598
- Cited by
- 109
- References
- 28
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 7 · 2023: 3 · 2022: 16 · 2021: 9 · 2020: 16 · 2019: 9 · 2018: 13 · 2017: 11 · 2016: 10 · 2015: 1
- FWCI
- 8.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Human Molecular Genetics (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by-nc)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Oxford University Press eBooks
- Funders
- Wellcome Trust (104116, 104116/Z/14/Z)
- Research Councils UK
- University of Edinburgh
- Medical Research Council (MR/K014137/1, MR/M006336/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- fragile X syndrome, FMRP, hippocampus, CA1 pyramidal neurons, dendritic spines, protein synthesis, synaptic plasticity, associative recognition memory, episodic-like memory, spatial memory, cross-species conservation, transgenic rats
- MeSH terms
- Animals, Disease Models, Animal, Female, Fragile X Syndrome, Hippocampus, Male, Memory Disorders, Neuronal Plasticity, Species Specificity, Rats, Sprague-Dawley, Pyramidal Cells, Maze Learning, Rats, Fragile X Mental Retardation Protein, Fragile X Messenger Ribonucleoprotein 1, Gene Knockout Techniques
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