ArticleLearning & memory (Cold Spring Harbor, N.Y.)2014
The eIF2α kinase PERK limits the expression of hippocampal metabotropic glutamate receptor-dependent long-term depression.
Article in Learning & memory (Cold Spring Harbor, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 71 citations in OpenAlex.
- Distinct cell type-specific mechanisms underlie cognitive dysfunction during persistent integrated stress response activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The ISR downstream effector ATF4 promotes mGluR-dependent long-term depression and associated behavior.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Astrocytic PERK Deficiency Drives Prefrontal Circuit Dysfunction and Depressive-Like Behaviors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Emerging roles for integrated stress response signaling in homeostasis.The FEBS journal · 2025Review
- Cerebellar output neurons can impair non-motor behaviors by altering development of extracerebellar connectivity.Nature communications · 2025Article
- The integrated stress response in brain diseases: A double-edged sword for proteostasis and synapses.Current opinion in neurobiology · 2024Review
- Cerebellar output neurons impair non-motor behaviors by altering development of extracerebellar connectivity.bioRxiv : the preprint server for biology · 2024Article
- A Ketogenic Diet may Improve Cognitive Function in Rats with Temporal Lobe Epilepsy by Regulating Endoplasmic Reticulum Stress and Synaptic Plasticity.Molecular neurobiology · 2024Article
- Patient-derived tau and amyloid-β facilitate long-term depressionBrain communications · 2024Article
- DYT-Frontiers in neuroscience · 2023Review
- Pathophysiology of stress granules: An emerging link to diseases (Review).International journal of molecular medicine · 2022Review
- Inhibition of the ISR abrogates mGluR5-dependent long-term depression and spatial memory deficits in a rat model of Alzheimer's disease.Translational psychiatry · 2022Article
- Long-Term Depression-Inducing Low Frequency Stimulation Enhances p-Tau181 and p-Tau217 in an Age-Dependent Manner in Live Rats.Journal of Alzheimer's disease : JAD · 2022Article
- Cell-type-specific disruption of PERK-eIF2α signaling in dopaminergic neurons alters motor and cognitive function.Molecular psychiatry · 2021Article
- Brain-specific suppression of AMPKα2 isoform impairs cognition and hippocampal LTP by PERK-mediated eIF2α phosphorylation.Molecular psychiatry · 2021Article
- Emerging and converging molecular mechanisms in dystonia.Journal of neural transmission (Vienna, Austria : 1996) · 2021Review
- Stress Responses in Down Syndrome Neurodegeneration: State of the Art and Therapeutic Molecules.Biomolecules · 2021Review
- UPF2 leads to degradation of dendritically targeted mRNAs to regulate synaptic plasticity and cognitive function.Molecular psychiatry · 2020Article
- The integrated stress response: From mechanism to disease.Science (New York, N.Y.) · 2020Review
- Cell-type-specific drug-inducible protein synthesis inhibition demonstrates that memory consolidation requires rapid neuronal translation.Nature neuroscience · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The proper regulation of translation is required for the expression of long-lasting synaptic plasticity. A major site of translational control involves the phosphorylation of eukaryotic initiation factor 2 α (eIF2α) by PKR-like endoplasmic reticulum (ER) kinase (PERK). To determine the role of PERK in hippocampal synaptic plasticity, we used the Cre-lox expression system to selectively disrupt PERK expression in the adult mouse forebrain. Here, we demonstrate that in hippocampal area CA1, metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD) is associated with increased eIF2α phosphorylation, whereas stimulation of early- and late-phase long-term potentiation (E-LTP and L-LTP, respectively) is associated with decreased eIF2α phosphorylation. Interesting, although PERK-deficient mice exhibit exaggerated mGluR-LTD, both E-LTP and L-LTP remained intact. We also found that mGluR-LTD is associated with a PERK-dependent increase in eIF2α phosphorylation. Our findings are consistent with the notion that eIF2α phosphorylation is a key site for the bidirectional control of persistent forms of synaptic LTP and LTD and suggest a distinct role for PERK in mGluR-LTD.
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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.