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Cited by 351Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchNeural dynamics and brain function

Memory formation depends on both synapse-specific modifications of synaptic strength and cell-specific increases in excitability

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Lisman, John, Cooper, Katherine, Sehgal, Megha, Silva, Alcino J.·2018·Nature Neuroscience
DOI 10.1038/s41593-018-0076-6PMC PMC5915620
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Abstract

The modification of synaptic strength produced by long-term potentiation (LTP) is widely thought to underlie memory storage. Indeed, given that hippocampal pyramidal neurons have >10,000 independently modifiable synapses, the potential for information storage by synaptic modification is enormous. However, recent work suggests that CREB-mediated global changes in neuronal excitability also play a critical role in memory formation. Because these global changes have a modest capacity for information storage compared with that of synaptic plasticity, their importance for memory function has been unclear. Here we review the newly emerging evidence for CREB-dependent control of excitability and discuss two possible mechanisms. First, the CREB-dependent transient change in neuronal excitability performs a memory-allocation function ensuring that memory is stored in ways that facilitate effective linking of events with temporal proximity (hours). Second, these changes may promote cell-assembly formation during the memory-consolidation phase. It has been unclear whether such global excitability changes and local synaptic mechanisms are complementary. Here we argue that the two mechanisms can work together to promote useful memory function.

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  • Synaptic network formation, maintenance and plasticity are closely linked to the intrinsic excitability of neurons, and their tight coordination and interdependence are foundational to cognitive processes such as memory and learning.

    “Synaptic network formation, maintenance and plasticity are all closely linked to the intrinsic excitability of neurons, and the tight coordination and interdependence of these phenomena are foundational to cognitive processes such as memory and learning (reviewed in 146).”

    From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [146]

    The Abstract and Discussion argue that synaptic plasticity and changes in neuronal excitability work together in memory formation. The Assembly consolidation hypothesis discusses forming and stabilizing memory ensembles, but presents excitability’s contribution to consolidation as a suggestion, not an established link to synaptic-network maintenance generally. The citing sentence overstates that part of the review. (LLM, conf=0.84)

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Authors
Lisman, J., Cooper, K., Sehgal, M., & Silva, A. J.
Affiliations
  • Brandeis University (US)
  • University of California, Los Angeles (US)
Corresponding author
Silva, Alcino J.
ORCID
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2018-02-12
Volume
21
Issue
3
Pages
309-314
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
DOI
10.1038/s41593-018-0076-6
PMC
PMC5915620
OpenAlex
W2789935103
Cited by
351
References
6
Citations by year
2026: 17 · 2025: 37 · 2024: 35 · 2023: 61 · 2022: 55 · 2021: 45 · 2020: 34 · 2019: 38 · 2018: 29
FWCI
4.87
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
  • National Institute on Aging (RF1AG013622)
  • National Institute of Mental Health (R01MH113071)
  • National Institute on Drug Abuse (R01DA043195)
  • National Institute of Neurological Disorders and Stroke (U01NS090583, R01NS103168, R56NS096710, U19NS104590, R01NS106969)
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
memory formation, long-term potentiation, synaptic plasticity, neuronal excitability, CREB, hippocampal pyramidal neurons, memory allocation, memory consolidation, cell assemblies, information storage
MeSH terms
Animals, Humans, Memory, Neuronal Plasticity, Neurons, Synapses, Cyclic AMP Response Element-Binding Protein, Long-Term Potentiation

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