Dopamine increases protein synthesis in hippocampal neurons enabling dopamine-dependent LTP
The reward and novelty-related neuromodulator dopamine plays an important role in hippocampal long-term memory, which is thought to involve protein-synthesis-dependent synaptic plasticity. However, the direct effects of dopamine on protein synthesis, and the functional implications of newly synthesi...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2025-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/100822 |
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| author | Tanja Fuchsberger Imogen Stockwell Matty Woods Zuzanna Brzosko Ingo H Greger Ole Paulsen |
| author_facet | Tanja Fuchsberger Imogen Stockwell Matty Woods Zuzanna Brzosko Ingo H Greger Ole Paulsen |
| author_sort | Tanja Fuchsberger |
| collection | DOAJ |
| description | The reward and novelty-related neuromodulator dopamine plays an important role in hippocampal long-term memory, which is thought to involve protein-synthesis-dependent synaptic plasticity. However, the direct effects of dopamine on protein synthesis, and the functional implications of newly synthesised proteins for synaptic plasticity, have not yet been investigated. We have previously reported that timing-dependent synaptic depression (t-LTD) can be converted into potentiation by dopamine application during synaptic stimulation (Brzosko et al., 2015) or postsynaptic burst activation (Fuchsberger et al., 2022). Here, we show that dopamine increases protein synthesis in mouse hippocampal CA1 neurons, enabling dopamine-dependent long-term potentiation (DA-LTP), which is mediated via the Ca2+-sensitive adenylate cyclase (AC) subtypes 1/8, cAMP, and cAMP-dependent protein kinase (PKA). We found that neuronal activity is required for the dopamine-induced increase in protein synthesis. Furthermore, dopamine induced a protein-synthesis-dependent increase in the AMPA receptor subunit GluA1, but not GluA2. We found that DA-LTP is absent in GluA1 knock-out mice and that it requires calcium-permeable AMPA receptors. Taken together, our results suggest that dopamine together with neuronal activity controls synthesis of plasticity-related proteins, including GluA1, which enable DA-LTP via a signalling pathway distinct from that of conventional LTP. |
| format | Article |
| id | doaj-art-39db1817c98a4f97b80eec8afd3a3658 |
| institution | DOAJ |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj-art-39db1817c98a4f97b80eec8afd3a36582025-08-20T02:48:09ZengeLife Sciences Publications LtdeLife2050-084X2025-03-011310.7554/eLife.100822Dopamine increases protein synthesis in hippocampal neurons enabling dopamine-dependent LTPTanja Fuchsberger0https://orcid.org/0000-0002-4751-8806Imogen Stockwell1https://orcid.org/0000-0002-9712-1700Matty Woods2Zuzanna Brzosko3Ingo H Greger4https://orcid.org/0000-0002-7291-2581Ole Paulsen5https://orcid.org/0000-0002-2258-5455Department of Physiology, Development and Neuroscience, Physiological Laboratory, University of Cambridge, Cambridge, United KingdomNeurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, United KingdomDepartment of Physiology, Development and Neuroscience, Physiological Laboratory, University of Cambridge, Cambridge, United KingdomDepartment of Physiology, Development and Neuroscience, Physiological Laboratory, University of Cambridge, Cambridge, United KingdomNeurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, United KingdomDepartment of Physiology, Development and Neuroscience, Physiological Laboratory, University of Cambridge, Cambridge, United KingdomThe reward and novelty-related neuromodulator dopamine plays an important role in hippocampal long-term memory, which is thought to involve protein-synthesis-dependent synaptic plasticity. However, the direct effects of dopamine on protein synthesis, and the functional implications of newly synthesised proteins for synaptic plasticity, have not yet been investigated. We have previously reported that timing-dependent synaptic depression (t-LTD) can be converted into potentiation by dopamine application during synaptic stimulation (Brzosko et al., 2015) or postsynaptic burst activation (Fuchsberger et al., 2022). Here, we show that dopamine increases protein synthesis in mouse hippocampal CA1 neurons, enabling dopamine-dependent long-term potentiation (DA-LTP), which is mediated via the Ca2+-sensitive adenylate cyclase (AC) subtypes 1/8, cAMP, and cAMP-dependent protein kinase (PKA). We found that neuronal activity is required for the dopamine-induced increase in protein synthesis. Furthermore, dopamine induced a protein-synthesis-dependent increase in the AMPA receptor subunit GluA1, but not GluA2. We found that DA-LTP is absent in GluA1 knock-out mice and that it requires calcium-permeable AMPA receptors. Taken together, our results suggest that dopamine together with neuronal activity controls synthesis of plasticity-related proteins, including GluA1, which enable DA-LTP via a signalling pathway distinct from that of conventional LTP.https://elifesciences.org/articles/100822dopaminesynaptic plasticityLTPCP-AMPARmemory |
| spellingShingle | Tanja Fuchsberger Imogen Stockwell Matty Woods Zuzanna Brzosko Ingo H Greger Ole Paulsen Dopamine increases protein synthesis in hippocampal neurons enabling dopamine-dependent LTP eLife dopamine synaptic plasticity LTP CP-AMPAR memory |
| title | Dopamine increases protein synthesis in hippocampal neurons enabling dopamine-dependent LTP |
| title_full | Dopamine increases protein synthesis in hippocampal neurons enabling dopamine-dependent LTP |
| title_fullStr | Dopamine increases protein synthesis in hippocampal neurons enabling dopamine-dependent LTP |
| title_full_unstemmed | Dopamine increases protein synthesis in hippocampal neurons enabling dopamine-dependent LTP |
| title_short | Dopamine increases protein synthesis in hippocampal neurons enabling dopamine-dependent LTP |
| title_sort | dopamine increases protein synthesis in hippocampal neurons enabling dopamine dependent ltp |
| topic | dopamine synaptic plasticity LTP CP-AMPAR memory |
| url | https://elifesciences.org/articles/100822 |
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