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Neuromodulation of hippocampal long-term synaptic plasticity

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Palacios-Filardo, Jon, Mellor, Jack R·2019·Current Opinion in Neurobiology
DOI 10.1016/j.conb.2018.08.009PMC PMC6367596
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Abstract

Multiple neuromodulators including acetylcholine, noradrenaline, dopamine and serotonin are released in response to uncertainty to focus attention on events where the predicted outcome does not match observed reality. In these situations, internal representations need to be updated, a process that requires long-term synaptic plasticity. Through a variety of common and divergent mechanisms, it is recently shown that all these neuromodulators facilitate the induction and/or expression of long-term synaptic plasticity within the hippocampus. Under physiological conditions, this may be critical for suprathreshold induction of plasticity endowing neuromodulators with a gating function and providing a mechanism by which neuromodulators enable the targeted updating of memory with relevant information to improve the accuracy of future predictions.

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  • Together, these designs could help test timing and patient-selection hypotheses, but they should not be presented as evidence that precision network therapeutics are already clinically reproducible.

    “Together, these designs could help test timing and patient-selection hypotheses, but they should not be presented as evidence that precision network therapeutics are already clinically reproducible [243,412].”

    From Synaptic Plasticity—Intrinsic Excitability and Antidepressant Discovery (2026) · cites this paper as [412]

    The ‘Similarity and divergence across neuromodulatory systems’ section (page unavailable) describes different timescales for neuromodulators’ effects on hippocampal plasticity, providing a basis for timing hypotheses. It does not discuss the proposed designs, patient selection, or whether precision network therapeutics are clinically reproducible; that clinical caution is not a finding reported by this source. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

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Authors
Palacios-Filardo, J., & Mellor, J. R.
Affiliations
University of Bristol (GB)
Corresponding author
Mellor, Jack R
ORCID
Mellor, Jack R
Venue
Current Opinion in Neurobiology
Publisher
Elsevier BV
Published
2019-02
Volume
54
Pages
37-43
ISSN
0959-4388 (ISSN-L)
DOI
10.1016/j.conb.2018.08.009
PMC
PMC6367596
OpenAlex
W2892198894
Cited by
184
References
9
Citations by year
2026: 19 · 2025: 23 · 2024: 30 · 2023: 26 · 2022: 27 · 2021: 27 · 2020: 22 · 2019: 9 · 2018: 1
FWCI
1.97
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Opinion in Neurobiology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Bristol Research (University of Bristol) (submittedVersion, cc-by)
  • Explore Bristol Research (submittedVersion, cc-by)
Funders
  • Wellcome Trust (101029/Z/13/Z)
  • Biotechnology and Biological Sciences Research Council (BB/R002177/1)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Keywords
neuromodulation, hippocampus, long-term synaptic plasticity, acetylcholine, norepinephrine, dopamine, serotonin, uncertainty, attention, memory updating, prediction
MeSH terms
Animals, Hippocampus, Humans, Neurons, Potassium Channels, Receptors, N-Methyl-D-Aspartate, Long-Term Potentiation, Neurotransmitter Agents

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