ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Aging-Related Hyperexcitability in CA3 Pyramidal Neurons Is Mediated by Enhanced A-Type K+ Channel Function and Expression.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 111 citations in OpenAlex.
- Age-related changes in behavioural and neural variability in a decision-making task.Nature communications · 2026Article
- Aged female and male C57BL/6J mice have reduced alcohol self-administration and altered acute alcohol withdrawal compared to younger animals.Frontiers in aging neuroscience · 2026Article
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- Cognitive outcomes of deep brain stimulation depend on age and hippocampal connectivity in Parkinson's and Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Unreliable homeostatic action potential broadening in cultured dissociated neurons.bioRxiv : the preprint server for biology · 2025Article
- Early signs of neuron autonomous and non-autonomous hyperexcitability in locus coeruleus noradrenergic neurons of a mouse model of tauopathy and Alzheimer's disease.Acta physiologica (Oxford, England) · 2025Article
- Age-related increase in the excitability of mouse layer V pyramidal neurons in the primary motor cortex is accompanied by an increased persistent inward current.GeroScience · 2025Article
- Aberrant neuronal hyperactivation causes an age-dependent behavioral decline inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Single-nucleotide polymorphism analysis accurately predicts multiple impairments in hippocampal activity and memory performance in a murine model of idiopathic autism.Scientific reports · 2025Article
- Cognitive enrichment improves spatial memory and alters hippocampal synaptic connectivity in a mouse model for early-life stress.Frontiers in cellular neuroscience · 2025Article
- Sympathetic motor neuron dysfunction is a missing link in age-associated sympathetic overactivity.eLife · 2024Article
- Sympathetic Motor Neuron Dysfunction is a Missing Link in Age-Associated Sympathetic Overactivity.bioRxiv : the preprint server for biology · 2024Article
- Delayed formation of neural representations of space in aged mice.Aging cell · 2023Article
- Optogenetic cleavage of the Miro GTPase reveals the direct consequences of real-time loss of function in Drosophila.PLoS biology · 2023Article
- Selective inhibition of somatostatin-positive dentate hilar interneurons induces age-related cellular changes and cognitive dysfunction.PNAS nexus · 2023Article
- Expression of the primate-specific LINC00473 RNA in mouse neurons promotes excitability and CREB-regulated transcription.The Journal of biological chemistry · 2023Article
- Delayed formation of neural representations of space in aged mice.bioRxiv : the preprint server for biology · 2023Article
- Blood-to-brain communication in aging and rejuvenation.Nature neuroscience · 2023Review
- Activation of Dopamine D2 Receptors Alleviates Neuronal Hyperexcitability in the Lateral Entorhinal Cortex via Inhibition of HCN Current in a Rat Model of Chronic Inflammatory Pain.Neuroscience bulletin · 2022Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Aging-related impairments in hippocampus-dependent cognition have been attributed to maladaptive changes in the functional properties of pyramidal neurons within the hippocampal subregions. Much evidence has come from work on CA1 pyramidal neurons, with CA3 pyramidal neurons receiving comparatively less attention despite its age-related hyperactivation being postulated to interfere with spatial processing in the hippocampal circuit. Here, we use whole-cell current-clamp to demonstrate that aged rat (29-32 months) CA3 pyramidal neurons fire significantly more action potentials (APs) during theta-burst frequency stimulation and that this is associated with faster AP repolarization (i.e., narrower AP half-widths and enlarged fast afterhyperpolarization). Using a combination of patch-clamp physiology, pharmacology, Western blot analyses, immunohistochemistry, and array tomography, we demonstrate that these faster AP kinetics are mediated by enhanced function and expression of Kv4.2/Kv4.3 A-type K(+) channels, particularly within the perisomatic compartment, of CA3 pyramidal neurons. Thus, our study indicates that inhibition of these A-type K(+) channels can restore the intrinsic excitability properties of aged CA3 pyramidal neurons to a young-like state. Significance statement: Age-related learning deficits have been attributed, in part, to altered hippocampal pyramidal neuronal function with normal aging. Much evidence has come from work on CA1 neurons, with CA3 neurons receiving comparatively less attention despite its age-related hyperactivation being postulated to interfere with spatial processing. Hence, we conducted a series of experiments to identify the cellular mechanisms that underlie the hyperexcitability reported in the CA3 region. Contrary to CA1 neurons, we demonstrate that postburst afterhyperpolarization is not altered with aging and that aged CA3 pyramidal neurons are able to fire significantly more action potentials and that this is associated with faster action potential repolarization through enhanced expression of Kv4.2/Kv4.3 A-type K(+) channels, particularly within the cell bodies of CA3 pyramidal neurons.
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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.