ArticleThe EMBO journal2013
REST/NRSF-mediated intrinsic homeostasis protects neuronal networks from hyperexcitability.
Article in The EMBO journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
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Who cites it
56 citing papers in PubMed, 105 citations in OpenAlex.
- Plasma REST: a novel candidate biomarker of Alzheimer's disease is modified by psychological intervention in an at-risk population.Translational psychiatry · 2017Trial
- Phosphorylation by CaMKIV regulates the transcriptional repressor activity and half-life of REST/NRSF.Science advances · 2026Article
- Harnessing metabolic control for synaptic stability: REST/NRSF links glycolytic inhibition to excitatory neurotransmission.The Journal of physiology · 2025Article
- Unreliable homeostatic action potential broadening in cultured dissociated neurons.bioRxiv : the preprint server for biology · 2025Article
- Hydrogen Peroxide-Induced Re-Expression of Repressor Element 1-Silencing Transcription Factor Contributes to Cardiac Vagal Dysfunction in Type 2 Diabetes Mellitus.Antioxidants (Basel, Switzerland) · 2025Article
- Neural Excitatory/Inhibitory Imbalance in Motor Aging: From Genetic Mechanisms to Therapeutic Challenges.Biology · 2025Review
- Dentate gyrus is needed for memory retrieval.Molecular psychiatry · 2024Article
- Restoring vision in adult amblyopia by enhancing plasticity through deletion of the transcriptional repressor REST.iScience · 2024Article
- Low glycemic index diet restrains epileptogenesis in a gender-specific fashion.Cellular and molecular life sciences : CMLS · 2023Article
- REST Is Not Resting: REST/NRSF in Health and Disease.Biomolecules · 2023Review
- Conditional knockout of REST/NRSF in excitatory neurons reduces seizure susceptibility to chemical kindling.Frontiers in cellular neuroscience · 2023Article
- Repressor element 1-silencing transcription factor deficiency yields profound hearing loss through KeLife · 2022Article
- A synthetic tear protein resolves dry eye through promoting corneal nerve regeneration.Cell reports · 2022Article
- IGF-1 receptor regulates upward firing rate homeostasis via the mitochondrial calcium uniporter.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Drug-resistant epilepsy: Drug target hypothesis and beyond the receptors.Epilepsia open · 2022Review
- Optogenetic Application to Investigating Cell Behavior and Neurological Disease.Frontiers in cellular neuroscience · 2022Review
- REST/NRSF drives homeostatic plasticity of inhibitory synapses in a target-dependent fashion.eLife · 2021Article
- Prenatal interleukin 6 elevation increases glutamatergic synapse density and disrupts hippocampal connectivity in offspring.Immunity · 2021Article
- Restoring neuronal chloride homeostasis with anti-NKCC1 gene therapy rescues cognitive deficits in a mouse model of Down syndrome.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- REST/NRSF deficiency impairs autophagy and leads to cellular senescence in neurons.Aging cell · 2021Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Intrinsic homeostasis enables neuronal circuits to maintain activity levels within an appropriate range by modulating neuronal voltage-gated conductances, but the signalling pathways involved in this process are largely unknown. We characterized the process of intrinsic homeostasis induced by sustained electrical activity in cultured hippocampal neurons based on the activation of the Repressor Element-1 Silencing Transcription Factor/Neuron-Restrictive Silencer Factor (REST/NRSF). We showed that 4-aminopyridine-induced hyperactivity enhances the expression of REST/NRSF, which in turn, reduces the expression of voltage-gated Na(+) channels, thereby decreasing the neuronal Na(+) current density. This mechanism plays an important role in the downregulation of the firing activity at the single-cell level, re-establishing a physiological spiking activity in the entire neuronal network. Conversely, interfering with REST/NRSF expression impaired this homeostatic response. Our results identify REST/NRSF as a critical factor linking neuronal activity to the activation of intrinsic homeostasis and restoring a physiological level of activity in the entire neuronal network.
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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.