Molecular mechanism of hippocampal long-term potentiation – Towards multiscale understanding of learning and memory
Open accessAbstract
Long-term potentiation (LTP) of synaptic transmission is considered to be a cellular counterpart of learning and memory. Activation of postsynaptic NMDA type glutamate receptor (NMDA-R) induces trafficking of AMPA type glutamate receptors (AMPA-R) and other proteins to the synapse in sequential fashion. At the same time, the dendritic spine expands for long-term and modulation of actin underlies this (structural LTP or sLTP). How these changes persist despite constant diffusion and turnover of the component proteins have been the central focus of the current LTP research. Signaling triggered by Ca 2+ -influx via NMDA-R triggers kinase including Ca 2+ /calmodulin-dependent protein kinase II (CaMKII). CaMKII can sustain longer-term biochemical signaling by forming a reciprocally-activating kinase-effector complex with its substrate proteins including Tiam1, thereby regulating persistence of the downstream signaling. Furthermore, activated CaMKII can condense at the synapse through the mechanism of liquid-liquid phase separation (LLPS). This increases the binding capacity at the synapse, thereby contributing to the maintenance of enlarged protein complexes. It may also serve as the synapse tag, which captures newly synthesized proteins.
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Long-term potentiation (LTP) is brief repetitive synaptic stimulation that results in long-lasting increases in synaptic strength.
“long-term potentiation (LTP), in which brief repetitive synaptic stimulation results in long-lasting increases in synaptic strength, was gaining popularity as a cellular model for learning and memory (16–22).”
From Synaptic memory and CaMKII (2023) · cites this paper as [21]
LTP expression is due to rapid postsynaptic accumulation of AMPARs.
“Thus, it is now generally accepted that LTP expression is due to the rapid postsynaptic accumulation of AMPARs.”
From Synaptic memory and CaMKII (2023) · cites this paper as [21]
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Nicoll, R. A., & Schulman, H. (2023) · Physiological Reviews · doi:10.1152/physrev.00034.2022 · Cited by 126 · see citing works
- Authors
- Hayashi, Y.
- Affiliations
- Kyoto University (JP)
- Corresponding author
- Hayashi, Yasunori
- ORCID
- Hayashi, Yasunori
- Venue
- Neuroscience Research
- Publisher
- Elsevier BV
- Published
- 2022-02
- Volume
- 175
- Pages
- 3-15
- ISSN
- 0168-0102 (ISSN-L)
- OpenAlex
- W3187600268
- Cited by
- 102
- References
- 28
- Citations by year
- 2026: 14 · 2025: 29 · 2024: 25 · 2023: 22 · 2022: 11 · 2021: 1
- FWCI
- 2.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuroscience Research (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- Takeda Science Foundation
- Core Research for Evolutional Science and Technology (JPMJCR20E4)
- Uehara Memorial Foundation
- NOVARTIS Foundation (Japan) for the Promotion of Science
- Human Frontier Science Program (RGP0020/2019, RGP0022/2013)
- Research Foundation for Opto-Science and Technology
- Japan Society for the Promotion of Science
- Ministry of Education, Culture, Sports, Science and Technology
- Naito Foundation
- Japan Science and Technology Agency
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- long-term potentiation, hippocampus, synaptic plasticity, learning and memory, NMDA receptor, AMPA receptor trafficking, dendritic spines, actin cytoskeleton, CaMKII, Tiam1, liquid-liquid phase separation, calcium signaling
- MeSH terms
- Hippocampus, Learning, Synapses, Long-Term Potentiation, Calcium-Calmodulin-Dependent Protein Kinase Type 2
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