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Entorhinal cortex directs learning-related changes in CA1 representations

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Grienberger, Christine, Magee, Jeffrey C.·2022·Nature
DOI 10.1038/s41586-022-05378-6PMC PMC9668747

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Abstract

Learning-related changes in brain activity are thought to underlie adaptive behaviours 1,2 . For instance, the learning of a reward site by rodents requires the development of an over-representation of that location in the hippocampus 3–6 . How this learning-related change occurs remains unknown. Here we recorded hippocampal CA1 population activity as mice learned a reward location on a linear treadmill. Physiological and pharmacological evidence suggests that the adaptive over-representation required behavioural timescale synaptic plasticity (BTSP) 7 . BTSP is known to be driven by dendritic voltage signals that we proposed were initiated by input from entorhinal cortex layer 3 (EC3). Accordingly, the CA1 over-representation was largely removed by optogenetic inhibition of EC3 activity. Recordings from EC3 neurons revealed an activity pattern that could provide an instructive signal directing BTSP to generate the over-representation. Consistent with this function, our observations show that exposure to a second environment possessing a prominent reward-predictive cue resulted in both EC3 activity and CA1 place field density that were more elevated at the cue than at the reward. These data indicate that learning-related changes in the hippocampus are produced by synaptic plasticity directed by an instructive signal from the EC3 that seems to be specifically adapted to the behaviourally relevant features of the environment.

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  • Plateau potentials on their own do not change synaptic strength.

    “These plateau potentials on their own do not change synaptic strength.”

    From Synaptic memory and CaMKII (2023) · cites this paper as [426]

    The Role of BTSP section (page not provided) says Ca2+ plateau potentials drive BTSP and can induce plasticity in a single trial, contrary to the claim that they do not change synaptic strength. The paper does not separately test a plateau in the absence of synaptic input, so its statement does not establish that plateaus are sufficient without input. (LLM, conf=0.79)

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  • Input to CA1 from entorhinal cortex provides an instructive signal in the form of large Ca2+-dependent dendritic plateau potentials.

    “Input to CA1 from entorhinal cortex provides an instructive signal in the form of large Ca2+-dependent dendritic plateau potentials (424, 426).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [426]

    The ‘Form of EC3 instructive signal’ section says EC3 input provides a target-like instructive signal and increases the probability of dendritic Ca2+ plateau potentials. It distinguishes that EC3 signal from the resulting plateaus, which function as local error signals in CA1; the claim conflates the two by saying the input provides its signal ‘in the form of’ plateau potentials. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Grienberger, C., & Magee, J. C.
Affiliations
Howard Hughes Medical Institute (US)
Corresponding author
Magee, Jeffrey C.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2022-11-02
Volume
611
Issue
7936
Pages
554-562
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/s41586-022-05378-6
PMC
PMC9668747
OpenAlex
W4307931716
Cited by
171
References
8
Citations by year
2026: 38 · 2025: 58 · 2024: 42 · 2023: 25 · 2022: 8
FWCI
17.15
Type
journal article
Language
en
Update notices
correction (2022-11-15)
Open access
Licence
Locations
  • Nature (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • Cullen Foundation
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
hippocampal CA1, optogenetic inhibition, reward-predictive cues, spatial learning
MeSH terms
Animals, Cues, Dendrites, Learning, Models, Neurological, Neuronal Plasticity, Neurons, Reward, Entorhinal Cortex, Mice, CA1 Region, Hippocampal, Optogenetics

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