ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2000
Abnormal synaptic plasticity and impaired spatial cognition in mice transgenic for exon 1 of the human Huntington's disease mutation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers.
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Who cites it
133 citing papers in PubMed, 400 citations in OpenAlex.
- Development of cognitive, motor, metabolic, and mutant huntingtin aggregation in the zQ175 mouse model of Huntington's disease.Scientific reports · 2025Article
- An integrated transcriptomic and proteomic map of the mouse hippocampus at synaptic resolution.Nature communications · 2025Article
- Restoring endogenous Dlg4/PSD95 expression by an artificial transcription factor ameliorates cognitive and motor learning deficits in the R6/2 mouse model of Huntington's disease.Clinical epigenetics · 2025Article
- AMPA receptor diffusional trapping machinery as an early therapeutic target in neurodegenerative and neuropsychiatric disorders.Translational neurodegeneration · 2025Review
- Neuroprotection by ADAM10 inhibition requires TrkB signaling in the Huntington's disease hippocampus.Cellular and molecular life sciences : CMLS · 2024Article
- BDNF and TRiC-inspired reagent rescue cortical synaptic deficits in a mouse model of Huntington's disease.Neurobiology of disease · 2024Article
- Exploring the Role of Neuroplasticity in Development, Aging, and Neurodegeneration.Brain sciences · 2023Review
- Exploration of the Shared Molecular Mechanisms between COVID-19 and Neurodegenerative Diseases through Bioinformatic Analysis.International journal of molecular sciences · 2023Article
- Huntingtin-associated protein 1-associated intracellular trafficking in neurodegenerative diseases.Frontiers in aging neuroscience · 2023Review
- Differential expression and roles of Huntingtin and Huntingtin-associated protein 1 in the mouse and primate brains.Cellular and molecular life sciences : CMLS · 2022Article
- Structural Plasticity of the Hippocampus in Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- Reduced expression of dopamine D2 receptors on astrocytes in R6/1 HD mice and HD post-mortem tissue.Neuroscience letters · 2022Article
- Neuroinflammation in Huntington's disease: From animal models to clinical therapeutics.Frontiers in immunology · 2022Review
- RTP801/REDD1 Is Involved in Neuroinflammation and Modulates Cognitive Dysfunction in Huntington's Disease.Biomolecules · 2021Article
- Mammalian/mechanistic target of rapamycin (mTOR) complexes in neurodegeneration.Molecular neurodegeneration · 2021Review
- Amyloid Prefibrillar Oligomers: The Surprising Commonalities in Their Structure and Activity.International journal of molecular sciences · 2021Review
- Neuron type-specific increase in lamin B1 contributes to nuclear dysfunction in Huntington's disease.EMBO molecular medicine · 2021Article
- A Mechanistic Model of NMDA and AMPA Receptor-Mediated Synaptic Transmission in Individual Hippocampal CA3-CA1 Synapses: A Computational Multiscale Approach.International journal of molecular sciences · 2021Article
- Nicotinamide Adenine Dinucleotide Phosphate Oxidases Are Everywhere in Brain Disease, but Not in Huntington's Disease?Frontiers in aging neuroscience · 2021Review
- Do Changes in Synaptic Autophagy Underlie the Cognitive Impairments in Huntington's Disease?Journal of Huntington's disease · 2021Review
73 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Huntington's disease (HD) is an autosomal dominant progressive and fatal neurodegenerative brain disorder caused by an expanded CAG/polyglutamine repeat in the coding region of the gene. Presymptomatic Huntington's disease patients often exhibit cognitive deficits before the onset of classical symptoms. To investigate the possibility that changes in synaptic plasticity might underlie cognitive impairment in HD, we examined hippocampal synaptic plasticity and spatial cognition in a transgenic mouse (R6/2 line) expressing exon 1 of the human Huntington's disease gene containing an expanded CAG repeat. This mouse exhibits a progressive and fatal neurological phenotype that resembles Huntington's disease. We report that R6/2 mice show marked alterations in synaptic plasticity at both CA1 and dentate granule cell synapses, and impaired spatial cognitive performance in the Morris water maze. The changes in hippocampal plasticity were age dependent, appearing at CA1 synapses several weeks before they were observed in the dentate gyrus. Deficits in synaptic plasticity at CA1 synapses occurred before an overt phenotype. This suggests that altered synaptic plasticity contributes to the pre-symptomatic changes in cognition reported in human carriers of the Huntington' disease gene. The temporal and regional changes in synaptic plasticity within the hippocampus mirror the appearance of neuronal intranuclear inclusions, suggesting a relationship between polyglutamine aggregation and dysfunction.
Indexed as
Identifiers
10864968PMC6772265W2125248031What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.