ArticleHippocampus2015
Combined administration of levetiracetam and valproic acid attenuates age-related hyperactivity of CA3 place cells, reduces place field area, and increases spatial information content in aged rat hippocampus.
Article in Hippocampus, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 53 citations in OpenAlex.
- Article
- An operant-based touchscreen morph discrimination task does not detect age-related mnemonic similarity deficits in rats.Oxford open neuroscience · 2026Article
- Age-dependent increases in dorsal hippocampal postsynaptic α5GABA-a receptors may be lost in a rat model of Alzheimer's disease.Scientific reports · 2025Article
- Age-related synaptic signatures of brain and cognitive reserve in the rat hippocampus and parahippocampal regions.Neurobiology of aging · 2025Article
- Ginkgo Biloba as a niche theme cognitive enhancer agent, 1420 dokumen of Scopus database. A bibliometric study from 1988 to 2024.F1000Research · 2025Article
- Hippocampal astrocytes induce sex-dimorphic effects on memory.Cell reports · 2024Article
- Cerebral hyperactivation across the Alzheimer's disease pathological cascade.Brain communications · 2024Review
- A long-term ketogenic diet in young and aged rats has dissociable effects on prelimbic cortex and CA3 ensemble activity.Frontiers in aging neuroscience · 2023Article
- Advanced age has dissociable effects on hippocampal CA1 ripples and CA3 high frequency events in male rats.Neurobiology of aging · 2022Article
- Loss of functional heterogeneity along the CA3 transverse axis in aging.Current biology : CB · 2022Article
- Aged Rats Exhibit Altered Behavior-Induced Oscillatory Activity, Place Cell Firing Rates, and Spatial Information Content in the CA1 Region of the Hippocampus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Dysregulation ofLearning & memory (Cold Spring Harbor, N.Y.) · 2022Article
- Probing the Neural Circuitry Targets of NeurotoxicantsFrontiers in toxicology · 2022Review
- Unilateral Perforant Path Transection Does Not Alter Lateral Entorhinal Cortical or Hippocampal CA3Frontiers in systems neuroscience · 2022Article
- Article
- Increased Hippocampal Excitability and Altered Learning Dynamics Mediate Cognitive Mapping Deficits in Human Aging.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Cognitive aging is associated with redistribution of synaptic weights in the hippocampus.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Heterogeneity of Age-Related Neural Hyperactivity along the CA3 Transverse Axis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Age and Ketogenic Diet Have Dissociable Effects on Synapse-Related Gene Expression Between Hippocampal Subregions.Frontiers in aging neuroscience · 2019Article
- The Antiepileptic Ketogenic Diet Alters Hippocampal Transporter Levels and Reduces Adiposity in Aged Rats.The journals of gerontology. Series A, Biological sciences and medical sciences · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Learning and memory deficits associated with age-related mild cognitive impairment have long been attributed to impaired processing within the hippocampus. Hyperactivity within the hippocampal CA3 region that is associated with aging is mediated in part by a loss of functional inhibitory interneurons and thought to underlie impaired performance in spatial memory tasks, including the abnormal tendency in aged animals to pattern complete spatial representations. Here, we asked whether the spatial firing patterns of simultaneously recorded CA3 and CA1 neurons in young and aged rats could be manipulated pharmacologically to selectively reduce CA3 hyperactivity and thus, according to hypothesis, the associated abnormality in spatial representations. We used chronically implanted high-density tetrodes to record the spatial firing properties of CA3 and CA1 units during animal exploration for food in familiar and novel environments. Aged CA3 place cells have higher firing rates, larger place fields, less spatial information content, and respond less to a change from a familiar to a novel environment than young CA3 cells. We also find that the combination of levetiracetam (LEV) + valproic acid (VPA), previously shown to act as a cognitive enhancer in tests of spatial memory, attenuate CA3 place cell firing rates, reduce place field area, and increase spatial information content in aged but not young adult rats. This is consistent with drug enhancing the specificity of neuronal firing with respect to spatial location. Contrary to expectation, however, LEV + VPA reduces place cell discrimination between novel and familiar environments, i.e., spatial correlations increase, independent of age even though drug enhances performance in cognitive tasks. The results demonstrate that spatial information content, or the number of bits of information encoded per action potential, may be the key correlate for enhancement of spatial memory by LEV + VPA.
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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.