Retinoic acid-gated BDNF synthesis in neuronal dendrites drives presynaptic homeostatic plasticity
Homeostatic synaptic plasticity is a non-Hebbian synaptic mechanism that adjusts synaptic strength to maintain network stability while achieving optimal information processing. Among the molecular mediators shown to regulate this form of plasticity, synaptic signaling through retinoic acid (RA) and...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/79863 |
| _version_ | 1797756115078873088 |
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| author | Shruti Thapliyal Kristin L Arendt Anthony G Lau Lu Chen |
| author_facet | Shruti Thapliyal Kristin L Arendt Anthony G Lau Lu Chen |
| author_sort | Shruti Thapliyal |
| collection | DOAJ |
| description | Homeostatic synaptic plasticity is a non-Hebbian synaptic mechanism that adjusts synaptic strength to maintain network stability while achieving optimal information processing. Among the molecular mediators shown to regulate this form of plasticity, synaptic signaling through retinoic acid (RA) and its receptor, RARα, has been shown to be critically involved in the homeostatic adjustment of synaptic transmission in both hippocampus and sensory cortices. In this study, we explore the molecular mechanism through which postsynaptic RA and RARα regulates presynaptic neurotransmitter release during prolonged synaptic inactivity at mouse glutamatertic synapses. We show that RARα binds to a subset of dendritically sorted brain-derived neurotrophic factor (Bdnf) mRNA splice isoforms and represses their translation. The RA-mediated translational de-repression of postsynaptic BDNF results in the retrograde activation of presynaptic tropomyosin receptor kinase B (TrkB) receptors, facilitating presynaptic homeostatic compensation through enhanced presynaptic release. Together, our study illustrates an RA-mediated retrograde synaptic signaling pathway through which postsynaptic protein synthesis during synaptic inactivity drives compensatory changes at the presynaptic site. |
| first_indexed | 2024-03-12T17:56:54Z |
| format | Article |
| id | doaj.art-d6e083534cee44ef9b14ceae095002f4 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-12T17:56:54Z |
| publishDate | 2022-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-d6e083534cee44ef9b14ceae095002f42023-08-02T14:31:07ZengeLife Sciences Publications LtdeLife2050-084X2022-12-011110.7554/eLife.79863Retinoic acid-gated BDNF synthesis in neuronal dendrites drives presynaptic homeostatic plasticityShruti Thapliyal0https://orcid.org/0000-0003-3531-3018Kristin L Arendt1Anthony G Lau2Lu Chen3https://orcid.org/0000-0002-8097-2699Departments of Neurosurgery, Neuropsychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, United StatesDepartments of Neurosurgery, Neuropsychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, United StatesDepartments of Neurosurgery, Neuropsychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, United StatesDepartments of Neurosurgery, Neuropsychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, United StatesHomeostatic synaptic plasticity is a non-Hebbian synaptic mechanism that adjusts synaptic strength to maintain network stability while achieving optimal information processing. Among the molecular mediators shown to regulate this form of plasticity, synaptic signaling through retinoic acid (RA) and its receptor, RARα, has been shown to be critically involved in the homeostatic adjustment of synaptic transmission in both hippocampus and sensory cortices. In this study, we explore the molecular mechanism through which postsynaptic RA and RARα regulates presynaptic neurotransmitter release during prolonged synaptic inactivity at mouse glutamatertic synapses. We show that RARα binds to a subset of dendritically sorted brain-derived neurotrophic factor (Bdnf) mRNA splice isoforms and represses their translation. The RA-mediated translational de-repression of postsynaptic BDNF results in the retrograde activation of presynaptic tropomyosin receptor kinase B (TrkB) receptors, facilitating presynaptic homeostatic compensation through enhanced presynaptic release. Together, our study illustrates an RA-mediated retrograde synaptic signaling pathway through which postsynaptic protein synthesis during synaptic inactivity drives compensatory changes at the presynaptic site.https://elifesciences.org/articles/79863homeostatic plasticityretrograde synaptic signalingRARαpresynaptic function |
| spellingShingle | Shruti Thapliyal Kristin L Arendt Anthony G Lau Lu Chen Retinoic acid-gated BDNF synthesis in neuronal dendrites drives presynaptic homeostatic plasticity eLife homeostatic plasticity retrograde synaptic signaling RARα presynaptic function |
| title | Retinoic acid-gated BDNF synthesis in neuronal dendrites drives presynaptic homeostatic plasticity |
| title_full | Retinoic acid-gated BDNF synthesis in neuronal dendrites drives presynaptic homeostatic plasticity |
| title_fullStr | Retinoic acid-gated BDNF synthesis in neuronal dendrites drives presynaptic homeostatic plasticity |
| title_full_unstemmed | Retinoic acid-gated BDNF synthesis in neuronal dendrites drives presynaptic homeostatic plasticity |
| title_short | Retinoic acid-gated BDNF synthesis in neuronal dendrites drives presynaptic homeostatic plasticity |
| title_sort | retinoic acid gated bdnf synthesis in neuronal dendrites drives presynaptic homeostatic plasticity |
| topic | homeostatic plasticity retrograde synaptic signaling RARα presynaptic function |
| url | https://elifesciences.org/articles/79863 |
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