ArticleFrontiers in molecular neuroscience2012
Conditional RARα knockout mice reveal acute requirement for retinoic acid and RARα in homeostatic plasticity.
Article in Frontiers in molecular neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- Dopaminergic tone inhibits spontaneous glutamate release and augments homeostatic synaptic plasticity.Molecular psychiatry · 2026Article
- Convergence and divergence of molecular mechanisms in Hebbian and homeostatic plasticity.Frontiers in synaptic neuroscience · 2026Review
- Retinoic acid-mediated homeostatic plasticity drives cell type-specific CP-AMPAR accumulation in nucleus accumbens core and incubation of cocaine craving.Molecular psychiatry · 2025Article
- Rapid homeostatic plasticity and neuropsychiatric therapeutics.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Review
- Retinoic acid-gated BDNF synthesis in neuronal dendrites drives presynaptic homeostatic plasticity.eLife · 2022Article
- Synthetic Retinoids Beyond Cancer Therapy.Annual review of pharmacology and toxicology · 2022Review
- Convergence of distinct signaling pathways on synaptic scaling to trigger rapid antidepressant action.Cell reports · 2021Article
- Clozapine modulates retinoid homeostasis in human brain and normalizes serum retinoic acid deficit in patients with schizophrenia.Molecular psychiatry · 2021Article
- FMRP Interacts with RARα in Synaptic Retinoic Acid Signaling and Homeostatic Synaptic Plasticity.International journal of molecular sciences · 2021Article
- Synaptic retinoic acid receptor signaling mediates mTOR-dependent metaplasticity that controls hippocampal learning.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Homeostatic synaptic plasticity as a metaplasticity mechanism - a molecular and cellular perspective.Current opinion in neurobiology · 2019Review
- Nuclear Receptors as Therapeutic Targets for Neurodegenerative Diseases: Lost in Translation.Annual review of pharmacology and toxicology · 2019Review
- Retinoic Acid Receptor RARα-Dependent Synaptic Signaling Mediates Homeostatic Synaptic Plasticity at the Inhibitory Synapses of Mouse Visual Cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- The fragile X mutation impairs homeostatic plasticity in human neurons by blocking synaptic retinoic acid signaling.Science translational medicine · 2018Article
- Postnatal Ablation of Synaptic Retinoic Acid Signaling Impairs Cortical Information Processing and Sensory Discrimination in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Neurogenesis in Response to Synthetic Retinoids at Different Temporal Scales.Molecular neurobiology · 2018Article
- Excessive UBE3A dosage impairs retinoic acid signaling and synaptic plasticity in autism spectrum disorders.Cell research · 2018Article
- Therapeutic potential of nuclear receptor agonists in Alzheimer's disease.Journal of lipid research · 2017Review
- A metaplasticity view of the interaction between homeostatic and Hebbian plasticity.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017Review
- Differential regulation of spontaneous and evoked inhibitory synaptic transmission in somatosensory cortex by retinoic acid.Synapse (New York, N.Y.) · 2016Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
All-trans retinoic acid (RA) plays important roles in brain development through regulating gene transcription. Recently, a novel post-developmental role of RA in mature brain was proposed. Specifically, RA rapidly enhanced excitatory synaptic transmission independent of transcriptional regulation. RA synthesis was induced when excitatory synaptic transmission was chronically blocked, and RA then activated dendritic protein synthesis and synaptic insertion of homomeric GluA1 AMPA receptors, thereby compensating for the loss of neuronal activity in a homeostatic fashion. This action of RA was suggested to be mediated by its canonical receptor RARα but no genetic evidence was available. Thus, we here tested the fundamental requirement of RARα in homeostatic plasticity using conditional RARα knockout (KO) mice, and additionally performed a structure-function analysis of RARα. We show that acutely deleting RARα in neurons eliminated RA's effect on excitatory synaptic transmission, and inhibited activity blockade-induced homeostatic synaptic plasticity. By expressing various RARα rescue constructs in RARα KO neurons, we found that the DNA-binding domain of RARα was dispensable for its role in regulating synaptic strength, further supporting the notion that RA and RARα act in a non-transcriptional manner in this context. By contrast, the ligand-binding domain (LBD) and the mRNA-binding domain (F-domain) are both necessary and sufficient for the function of RARα in homeostatic plasticity. Furthermore, we found that homeostatic regulation performed by the LBD/F-domains leads to insertion of calcium-permeable AMPA receptors. Our results confirm with unequivocal genetic approaches that RA and RARα perform essential non-transcriptional functions in regulating synaptic strength, and establish a functional link between the various domains of RARα and their involvement in regulating protein synthesis and excitatory synaptic transmission during homeostatic plasticity.
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