ArticleProceedings of the National Academy of Sciences of the United States of America2021
Cognitive aging is associated with redistribution of synaptic weights in the hippocampus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 56 citations in OpenAlex.
- Metabotropic glutamate receptor 5 is associated with plasma GFAP dependent on age.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Consciousness, subjectivity, and aging in western thought.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- ACSS2 upregulation enhances neuronal resilience to aging and tau-associated neurodegeneration.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Effect of Proximity to Failure in Resistance Training on Circulating Levels of Neuroprotective Biomarkers.Biology · 2025Article
- The Drosophila escape motor circuit shows differential vulnerability to aging linked to functional decay.PLoS biology · 2025Article
- Chronic optogenetic activation of hippocampal CA1 neurons triggers Alzheimer's disease-like proteomic remodeling.iScience · 2025Article
- Exercise-induced irisin ameliorates cognitive impairment following chronic cerebral hypoperfusion by suppressing neuroinflammation and hippocampal neuronal apoptosis.Journal of neuroinflammation · 2025Article
- Gastrointestinal exposure to silica nanoparticles induced Alzheimer's disease-like neurotoxicity in mice relying on gut microbiota and modulation through TLR4/NF-κB and HDAC.Journal of nanobiotechnology · 2025Article
- Article
- Age-related synaptic signatures of brain and cognitive reserve in the rat hippocampus and parahippocampal regions.Neurobiology of aging · 2025Article
- Independent associations of sleep and physical activity with cognition are mediated by hippocampal microstructure in middle-aged and older adults.Neurobiology of aging · 2025Article
- Modeling early phenotypes of Parkinson's disease by age-induced midbrain-striatum assembloids.Communications biology · 2024Article
- Regulation of synapse density by Pumilio RNA-binding proteins.Cell reports · 2024Article
- Alzheimer's-linked axonal changes accompany elevated antidromic action potential failure rate in aged mice.Brain research · 2024Article
- Early hippocampal hyperexcitability and synaptic reorganization in mouse models of amyloidosis.iScience · 2024Article
- Harnessing BDNF Signaling to Promote Resilience in Aging.Aging and disease · 2024Review
- Intermittent working memory training during adulthood protects against age-related long-term spatial reference memory decline in rats.GeroScience · 2024Article
- Changes in microstructural similarity of hippocampal subfield circuits in pathological cognitive aging.Brain structure & function · 2024Article
- Genetic context drives age-related disparities in synaptic maintenance and structure across cortical and hippocampal neuronal circuits.Aging cell · 2024Article
- Cerebral hyperactivation across the Alzheimer's disease pathological cascade.Brain communications · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 3 institutions in 1 country.
Funding
Abstract
Behaviors that rely on the hippocampus are particularly susceptible to chronological aging, with many aged animals (including humans) maintaining cognition at a young adult-like level, but many others the same age showing marked impairments. It is unclear whether the ability to maintain cognition over time is attributable to brain maintenance, sufficient cognitive reserve, compensatory changes in network function, or some combination thereof. While network dysfunction within the hippocampal circuit of aged, learning-impaired animals is well-documented, its neurobiological substrates remain elusive. Here we show that the synaptic architecture of hippocampal regions CA1 and CA3 is maintained in a young adult-like state in aged rats that performed comparably to their young adult counterparts in both trace eyeblink conditioning and Morris water maze learning. In contrast, among learning-impaired, but equally aged rats, we found that a redistribution of synaptic weights amplifies the influence of autoassociational connections among CA3 pyramidal neurons, yet reduces the synaptic input onto these same neurons from the dentate gyrus. Notably, synapses within hippocampal region CA1 showed no group differences regardless of cognitive ability. Taking the data together, we find the imbalanced synaptic weights within hippocampal CA3 provide a substrate that can explain the abnormal firing characteristics of both CA3 and CA1 pyramidal neurons in aged, learning-impaired rats. Furthermore, our work provides some clarity with regard to how some animals cognitively age successfully, while others' lifespans outlast their "mindspans."
Indexed as
Identifiers
What Socratic 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 Socratic graph.