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Cited by 769Memory and Neural MechanismsNeural dynamics and brain functionNeuroscience and Neuropharmacology Research

Graded persistent activity in entorhinal cortex neurons

Egorov, Alexei V., Hamam, Bassam N., Fransén, Erik, Hasselmo, Michael E., Alonso, Angel A.·2002·Nature
DOI 10.1038/nature01171
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Abstract

Working memory represents the ability of the brain to hold externally or internally driven information for relatively short periods of time. Persistent neuronal activity is the elementary process underlying working memory but its cellular basis remains unknown. The most widely accepted hypothesis is that persistent activity is based on synaptic reverberations in recurrent circuits. The entorhinal cortex in the parahippocampal region is crucially involved in the acquisition, consolidation and retrieval of long-term memory traces for which working memory operations are essential. Here we show that individual neurons from layer V of the entorhinal cortex-which link the hippocampus to extensive cortical regions-respond to consecutive stimuli with graded changes in firing frequency that remain stable after each stimulus presentation. In addition, the sustained levels of firing frequency can be either increased or decreased in an input-specific manner. This firing behaviour displays robustness to distractors; it is linked to cholinergic muscarinic receptor activation, and relies on activity-dependent changes of a Ca2+-sensitive cationic current. Such an intrinsic neuronal ability to generate graded persistent activity constitutes an elementary mechanism for working memory.

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Crossref · 10.1038/nature01171

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  • The EC is known to have higher energy demands and to be more metabolically active than many other brain regions.

    “As such, it is known to have higher energy demands and to be more metabolically active that many other brain regions75.”

    From APOE4 is Associated with Differential Regional Vulnerability to Bioenergetic Deficits in Aged APOE Mice (2020) · cites this paper as [75]

  • ACh enhances persistent spiking or plateau potentials within cortical structures, as demonstrated in brain slice preparations of the entorhinal cortex, prefrontal cortex, postsubiculum and perirhinal cortex.

    “ACh enhances persistent spiking or plateau potentials within cortical structures, as demonstrated in brain slice preparations of the entorhinal cortex (Klink and Alonso, 1997; Egorov et al., 2002; Fransen et al., 2006; Tahvildari et al., 2007), prefrontal cortex (Haj-Dahmane and Andrade, 1996, 1997, 1998), postsubiculum (Yoshida and Hasselmo, 2009) and perirhinal cortex (Leung et al., 2006).”

    From Modes and models of forebrain cholinergic neuromodulation of cognition (2011) · cites this paper as Egorov et al., 2002

  • The cholinergic enhancement of persistent spiking is reduced by muscarinic antagonists such as scopolamine, indicating a dependence on mechanisms activated by mAChRs.

    “The cholinergic enhancement of persistent spiking is reduced by muscarinic antagonists such as scopolamine, indicating a dependence on mechanisms activated by mAChRs (Klink and Alonso 1997; Egorov et al, 2002; Yoshida and Hasselmo, 2009).”

    From Modes and models of forebrain cholinergic neuromodulation of cognition (2011) · cites this paper as Egorov et al, 2002

  • Persistent spiking appears to result from muscarinic receptor activation of a calcium-sensitive non-specific cation current I(CAN).

    “Persistent spiking appears to result from muscarinic receptor activation of a calcium-sensitive non-specific cation current I(CAN) (Egorov et al., 2002; Shalinsky et al., 2002; Fransen et al., 2006).”

    From Modes and models of forebrain cholinergic neuromodulation of cognition (2011) · cites this paper as Egorov et al., 2002

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Authors
Egorov, A. V., Hamam, B. N., Fransén, E., Hasselmo, M. E., & Alonso, A. A.
Affiliations
  • Montreal Neurological Institute and Hospital (CA)
  • KTH Royal Institute of Technology (SE)
  • Boston University (US)
Corresponding author
Alonso, Angel A.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2002-11
Volume
420
Issue
6912
Pages
173-178
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature01171
OpenAlex
W2023699349
Cited by
769
References
50
Citations by year
2026: 9 · 2025: 16 · 2024: 26 · 2023: 24 · 2022: 19 · 2021: 26 · 2020: 25 · 2019: 25 · 2018: 44 · 2017: 19 · 2016: 19 · 2015: 36 · 2014: 47 · 2013: 39 · 2012: 37
FWCI
20.04
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
persistent neuronal activity, working memory, entorhinal cortex, recurrent circuits, muscarinic receptors, cholinergic modulation, intrinsic excitability, distractor robustness
MeSH terms
Action Potentials, Animals, Calcium, Electric Conductivity, Hippocampus, Male, Memory, Short-Term, Models, Neurological, Neurons, Synapses, Entorhinal Cortex, Rats, Long-Evans, Calcium Channels, L-Type, Rats, In Vitro Techniques

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