Locus coeruleus input to hippocampal CA3 drives single-trial learning of a novel context
Open accessAbstract
Significance: The ability to remember a new place is crucial for survival. The locus coeruleus (LC) in the brain stem is known to respond to novel sensory stimuli and can facilitate hippocampus-dependent memory, although the circuit and the role that LC plays in novelty-associated memory is unknown. We performed circuit-specific optogenetic inhibition and found that the hippocampal CA3 subregion is the crucial target of LC projections during the encoding of a novel context. Furthermore, we show with activity-dependent labeling and in vivo calcium imaging that LC inputs are necessary to provide stable neuronal representations of the context. This study provides evidence that LC neuromodulation, especially to the CA3 subregion, plays a crucial role in memory formation of a new context.
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Stimulation of locus coeruleus neurons enhances hippocampus-dependent memory.
“Notably, stimulation of locus coeruleus neurons, presumably releasing noradrenaline or dopamine, enhances hippocampus-dependent memory [105–108].”
From Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons (2024) · cites this paper as [107]
Cites
McClelland, J. L., McNaughton, B. L., & O'Reilly, R. C. (1995) · Psychological Review · doi:10.1037/0033-295x.102.3.419 · Cited by 5,256 · see citing works
Simple memory: a theory for archicortex
Marr, D. (1971) · Philosophical Transactions of the Royal Society of London. B, Biological Sciences · doi:10.1098/rstb.1971.0078 · Cited by 2,771 · see citing works
The hippocampal-VTA loop: controlling the entry of information into long-term memory
Lisman, J. E., & Grace, A. A. (2005) · Neuron · doi:10.1016/j.neuron.2005.05.002 · Cited by 1,983 · see citing works
Kempadoo, K. A., Mosharov, E. V., Choi, S. J., Sulzer, D., & Kandel, E. R. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1616515114 · Cited by 647 · see citing works
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Locus coeruleus: a new look at the blue spot
Poe, G. R., Foote, S., Eschenko, O., Johansen, J. P., Bouret, S., Aston-Jones, G., Harley, C. W., Manahan-Vaughan, D., Weinshenker, D., Valentino, R., et al. (2020) · Nature Reviews Neuroscience · doi:10.1038/s41583-020-0360-9 · Cited by 720 · see citing works
Hippocampal CA2 sharp-wave ripples reactivate and promote social memory
Oliva, A., Fernández-Ruiz, A., Leroy, F., & Siegelbaum, S. A. (2020) · Nature · doi:10.1038/s41586-020-2758-y · Cited by 268 · see citing works
Kaufman, A. M., Geiller, T., & Losonczy, A. (2020) · Neuron · doi:10.1016/j.neuron.2019.12.029 · Cited by 193 · see citing works
Swift, K. M., Gross, B. A., Frazer, M. A., Bauer, D. S., Clark, K. J. D., Vazey, E. M., Aston-Jones, G., Li, Y., Pickering, A. E., Sara, S. J., et al. (2018) · Current Biology · doi:10.1016/j.cub.2018.09.054 · Cited by 158 · see citing works
Zhang, H., Chaudhury, D., Nectow, A. R., Friedman, A. K., Zhang, S., Juarez, B., Liu, H., Pfau, M. L., Aleyasin, H., Jiang, C., et al. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.08.020 · Cited by 88 · see citing works
Kim, O., Okamoto, Y., Kaufmann, W. A., Brose, N., Shigemoto, R., & Jonas, P. (2024) · PLOS Biology · doi:10.1371/journal.pbio.3002879 · Cited by 15 · see citing works
The Functions of Dopamine in Operant Conditioned Reflexes
Maiorov, V. I. (2019) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-019-00815-y · Cited by 10 · see citing works
- Authors
- Wagatsuma, A., Okuyama, T., Sun, C., Smith, L. M., Abe, K., & Tonegawa, S.
- Affiliations
- Massachusetts Institute of Technology (US)
- RIKEN BioResource Research Center (JP)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Tonegawa, Susumu
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-12-26
- Volume
- 115
- Issue
- 2
- Pages
- E310-E316
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5777050
- OpenAlex
- W2776257264
- Cited by
- 283
- References
- 4
- Citations by year
- 2026: 16 · 2025: 38 · 2024: 44 · 2023: 49 · 2022: 29 · 2021: 26 · 2020: 34 · 2019: 26 · 2018: 19
- FWCI
- 12.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- RIKEN Brain Science Institute (N/A)
- Howard Hughes Medical Institute (N/A)
- JPB Foundation (N/A)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- locus coeruleus, hippocampal CA3, one-trial learning, novel context, contextual memory, neuromodulation, memory reactivation, place fields, CA1, dentate gyrus, memory encoding
- MeSH terms
- Animals, Behavior, Animal, Calcium, Hippocampus, Locus Coeruleus, Male, Memory, Neural Pathways, Neurons, Temporal Lobe, Dentate Gyrus, Mice
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