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Cited by 397Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersNeural dynamics and brain function

Synaptic Signaling by All-Trans Retinoic Acid in Homeostatic Synaptic Plasticity

Open access
Aoto, Jason, Nam, Christine I., Poon, Michael M., Ting, Pamela, Chen, Lu·2008·Neuron
DOI 10.1016/j.neuron.2008.08.012PMC PMC2634746
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Abstract

Normal brain function requires that the overall synaptic activity in neural circuits be kept constant. Long-term alterations of neural activity lead to homeostatic regulation of synaptic strength by a process known as synaptic scaling. The molecular mechanisms underlying synaptic scaling are largely unknown. Here, we report that all-trans retinoic acid (RA), a well-known developmental morphogen, unexpectedly mediates synaptic scaling in response to activity blockade. We show that activity blockade increases RA synthesis in neurons and that acute RA treatment enhances synaptic transmission. The RA-induced increase in synaptic strength is occluded by activity blockade-induced synaptic scaling. Suppression of RA synthesis prevents synaptic scaling. This form of RA signaling operates via a translation-dependent but transcription-independent mechanism, causes an upregulation of postsynaptic glutamate receptor levels, and requires RARalpha receptors. Together, our data suggest that RA functions in homeostatic plasticity as a signaling molecule that increases synaptic strength by a protein synthesis-dependent mechanism.

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  • Extranuclear RARα acts as a sensor to the compensatory increased levels of RA generated upon neuronal activity for safeguarding information and homeostatic plasticity.

    “Nevertheless, it highlights a novel pool of extranuclear RAR ␣ as a sensor to the compensatory increased levels of RA generated upon neuronal activity for safeguarding information and homeostatic plasticity ( 160, 161 ).”

    From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [160]

    The Results locate RARα in dendrites, and the Discussion says RA signaling in this form of homeostatic plasticity requires dendritically localized RARα. The paper also links homeostatic plasticity to maintaining neural-circuit stability and coding capacity. However, it reports increased RA production after neuronal activity blockade, not upon increased neuronal activity; it does not directly establish RARα as a sensor that safeguards information. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Enhanced AMPAR accumulation under conditions of both action potential and NMDAR block involves local synthesis and insertion of GluA1-containing/GluA2-lacking AMPAR into synapses, so that the synaptic composition of AMPAR is modified.

    “Enhanced AMPAR accumulation under conditions of both action potential and NMDAR block involves local synthesis and insertion of GluA1-containing/GluA2-lacking AMPAR into synapses, so that the synaptic composition of AMPAR is modified (Ju et al. 2004;Sutton et al. 2006;Aoto et al. 2008).”

    From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Aoto et al. 2008

  • Enhanced GluA1 synthesis and accumulation induced by TTX + APV is mediated through production of retinoic acid and activation of the RA receptor RARa.

    “It has recently been suggested that the enhanced GluA1 synthesis and accumulation induced by TTX þ APV is mediated through production of retinoic acid (RA) and activation of the RA receptor RARa, as suppressing RA production or RARa receptors blocks the effects of TTX þ APV, and RA can stimulate local translation of GluA1 (Aoto et al. 2008;Poon and Chen 2008).”

    From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Aoto et al. 2008

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Authors
Aoto, J., Nam, C. I., Poon, M. M., Ting, P., & Chen, L.
Affiliations
University of California, Berkeley (US)
Corresponding author
Chen, Lu
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2008-10
Volume
60
Issue
2
Pages
308-320
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2008.08.012
PMC
PMC2634746
OpenAlex
W2050519369
Cited by
397
References
62
Citations by year
2026: 11 · 2025: 21 · 2024: 18 · 2023: 20 · 2022: 29 · 2021: 32 · 2020: 19 · 2019: 29 · 2018: 19 · 2017: 20 · 2016: 15 · 2015: 27 · 2014: 16 · 2013: 32 · 2012: 27
FWCI
8.94
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • W. M. Keck Foundation
  • Arnold and Mabel Beckman Foundation
  • David and Lucile Packard Foundation
  • National Institute of Mental Health
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Keywords
all-trans retinoic acid, homeostatic plasticity, synaptic scaling, synaptic transmission, retinoic acid synthesis, postsynaptic glutamate receptors, protein synthesis, synaptic homeostasis
MeSH terms
Retinoic Acid Receptor alpha, Animals, Cells, Cultured, Hippocampus, Homeostasis, Immunohistochemistry, Synaptic Transmission, Neuronal Plasticity, Organ Culture Techniques, Transfection, Protein Biosynthesis, Tretinoin, Signal Transduction, Up-Regulation, Pyramidal Cells, Receptors, AMPA, Receptors, Retinoic Acid, Patch-Clamp Techniques, RNA, Small Interfering, Rats

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