ArticleProceedings of the National Academy of Sciences of the United States of America2019
Synaptic retinoic acid receptor signaling mediates mTOR-dependent metaplasticity that controls hippocampal learning.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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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.
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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.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Pooled it
- Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026Review
- Enriched Environment Enhances Motor Function in Mice With Cerebral Infarction by Promoting mTOR-Dependent Autophagy in the Contralateral Dentate Nucleus.The Kaohsiung journal of medical sciences · 2026Article
- ALDH2-mediated GABA biosynthesis regulates hippocampal LTP and learning adaptability.Nature chemical biology · 2026Article
- Convergence and divergence of molecular mechanisms in Hebbian and homeostatic plasticity.Frontiers in synaptic neuroscience · 2026Review
- Orphan Receptor GPRC5B Controls Adult Hippocampal Neurogenesis and Affects Retinoic Acid-Mediated Behaviors.Molecular neurobiology · 2025Article
- Cingulate retinoic acid signaling regulates neuropathic pain and comorbid anxiodepression via extracellular matrix homeostasis.The Journal of clinical investigation · 2025Article
- Retinoic acid-mediated homeostatic plasticity drives cell type-specific CP-AMPAR accumulation in nucleus accumbens core and incubation of cocaine craving.Molecular psychiatry · 2025Article
- Potential therapeutic effects of ibudilast and retinoic acid against cuprizone-induced behavioral and biochemical changes in mouse brain.Frontiers in molecular neuroscience · 2025Article
- Neuroplasticity in autism spectrum disorder: a systematic review.Dementia & neuropsychologia · 2025Review
- Synaptic transmission in supragranular layers of the human cortex - comparative review of structure, function, and plasticity.Frontiers in synaptic neuroscience · 2025Review
- Retinoic acid-mediated homeostatic plasticity in the nucleus accumbens core contributes to incubation of cocaine craving.Psychopharmacology · 2024Article
- Ketamine induced synaptic plasticity operates independently of long-term potentiation.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- The level of protein in the maternal murine diet modulates the facial appearance of the offspring via mTORC1 signaling.Nature communications · 2024Article
- Retinoic acid modulation of granule cell activity and spatial discrimination in the adult hippocampus.Frontiers in cellular neuroscience · 2024Article
- Neuroprotective effects of ellorarxine in neuronal models of degeneration.Frontiers in neuroscience · 2024Article
- The Contribution of Hippocampal All-Trans Retinoic Acid (ATRA) Deficiency to Alzheimer's Disease: A Narrative Overview of ATRA-Dependent Gene Expression in Post-Mortem Hippocampal Tissue.Antioxidants (Basel, Switzerland) · 2023Review
- Insufficient support for retinoic acid receptor control of synaptic plasticity through a non-genomic mechanism.Frontiers in neuroendocrinology · 2023Review
- Retinoid homeostasis in major depressive disorder.Translational psychiatry · 2023Article
- Neuromodulation: Actions of Dopamine, Retinoic Acid, Nitric Oxide, and Other Substances on Retinal Horizontal Cells.Eye and brain · 2023Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Homeostatic synaptic plasticity is a stabilizing mechanism engaged by neural circuits in response to prolonged perturbation of network activity. The non-Hebbian nature of homeostatic synaptic plasticity is thought to contribute to network stability by preventing "runaway" Hebbian plasticity at individual synapses. However, whether blocking homeostatic synaptic plasticity indeed induces runaway Hebbian plasticity in an intact neural circuit has not been explored. Furthermore, how compromised homeostatic synaptic plasticity impacts animal learning remains unclear. Here, we show in mice that the experience of an enriched environment (EE) engaged homeostatic synaptic plasticity in hippocampal circuits, thereby reducing excitatory synaptic transmission. This process required RARα, a nuclear retinoic acid receptor that doubles as a cytoplasmic retinoic acid-induced postsynaptic regulator of protein synthesis. Blocking RARα-dependent homeostatic synaptic plasticity during an EE experience by ablating RARα signaling induced runaway Hebbian plasticity, as evidenced by greatly enhanced long-term potentiation (LTP). As a consequence, RARα deletion in hippocampal circuits during an EE experience resulted in enhanced spatial learning but suppressed learning flexibility. In the absence of RARα, moreover, EE experience superactivated mammalian target of rapamycin (mTOR) signaling, causing a shift in protein translation that enhanced the expression levels of AMPA-type glutamate receptors. Treatment of mice with the mTOR inhibitor rapamycin during an EE experience not only restored normal AMPA-receptor expression levels but also reversed the increases in runaway Hebbian plasticity and learning after hippocampal RARα deletion. Thus, our findings reveal an RARα- and mTOR-dependent mechanism by which homeostatic plasticity controls Hebbian plasticity and learning.
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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.