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Cited by 60Neuroscience and Neuropharmacology ResearchVisual perception and processing mechanismsTreatment of Major Depression

Subanesthetic Ketamine Reactivates Adult Cortical Plasticity to Restore Vision from Amblyopia

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Grieco, Steven F., Qiao, Xin, Zheng, Xiaoting, Liu, Yongjun, Chen, Lujia, Zhang, Hai, Yu, Zhaoxia, Gavornik, Jeffrey P. +4 more·2020·Current Biology
DOI 10.1016/j.cub.2020.07.008PMC PMC7925140

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Abstract

Subanesthetic ketamine evokes rapid and long-lasting antidepressant effects in human patients. The mechanism for ketamine's effects remains elusive, but ketamine may broadly modulate brain plasticity processes. We show that single-dose ketamine reactivates adult mouse visual cortical plasticity and promotes functional recovery of visual acuity defects from amblyopia. Ketamine specifically induces downregulation of neuregulin-1 (NRG1) expression in parvalbumin-expressing (PV) inhibitory neurons in mouse visual cortex. NRG1 downregulation in PV neurons co-tracks both the fast onset and sustained decreases in synaptic inhibition to excitatory neurons, along with reduced synaptic excitation to PV neurons in vitro and in vivo following a single ketamine treatment. These effects are blocked by exogenous NRG1 as well as PV targeted receptor knockout. Thus, ketamine reactivation of adult visual cortical plasticity is mediated through rapid and sustained cortical disinhibition via downregulation of PV-specific NRG1 signaling. Our findings reveal the neural plasticity-based mechanism for ketamine-mediated functional recovery from adult amblyopia.

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  • Low-dose ketamine treatment reduces L2/3 PV cell activity by reducing the strength of their L4 excitatory inputs, resulting in increases in excitatory neuron responses in L2/3 of bV1, consistent with a PV-mediated cortical disinhibitory mechanism.

    “Low-dose ketamine treatment reduces L2/3 PV cell activity by reducing the strength of their L4 excitatory inputs, resulting in increases in excitatory neuron responses in L2/3 of bV1, consistent with a PV-mediated cortical disinhibitory mechanism (Grieco et al., 2020(Grieco et al., , 2021)).”

    From Psychedelics and Neural Plasticity: Therapeutic Implications (2022) · cites this paper as Grieco et al., 2020

  • Ketamine's promotion of ODP and recovery from amblyopia is dependent on neuregulin-1 (NRG1) and ErbB4 signaling by PV cells.

    “Ketamine also promotes ODP and recovery from amblyopia in adult animals, and all of this is dependent on neuregulin-1 (NRG1) and ErbB4 signaling by PV cells (Grieco et al., 2020).”

    From Psychedelics and Neural Plasticity: Therapeutic Implications (2022) · cites this paper as Grieco et al., 2020

  • Ketamine promotes ocular dominance plasticity in the binocular primary visual cortex (bV1).

    “The ability of ketamine to promote ODP in the binocular primary visual cortex (bV1) has recently been reported (Grieco et al., 2020;Casarotto et al., 2021, Cannarozzo et al., 2022).”

    From Psychedelics and Neural Plasticity: Therapeutic Implications (2022) · cites this paper as Grieco et al., 2020

  • Ketamine promotes ODP and recovery from amblyopia in adult animals.

    “Ketamine also promotes ODP and recovery from amblyopia in adult animals, and all of this is dependent on neuregulin-1 (NRG1) and ErbB4 signaling by PV cells (Grieco et al., 2020).”

    From Psychedelics and Neural Plasticity: Therapeutic Implications (2022) · cites this paper as Grieco et al., 2020

  • Reopening of critical periods in adulthood has been shown for several pharmacological manipulations, including fluoxetine, ketamine, R,R-HNK, and MDMA.

    “An example of this is the reopening of critical periods in adulthood which has been shown for a number of pharmacological manipulations, including fluoxetine (Maya Vetencourt et al., 2008;Karpova et al., 2011), ketamine (Grieco et al., 2020;Casarotto et al., 2021), R,R-HNK (Cannarozzo et al., 2022), and MDMA (Nardou et al., 2019).”

    From Psychedelics and Neural Plasticity: Therapeutic Implications (2022) · cites this paper as Grieco et al., 2020

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Cited by

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Authors
Grieco, S. F., Qiao, X., Zheng, X., Liu, Y., Chen, L., Zhang, H., Yu, Z., Gavornik, J. P., Lai, C., Gandhi, S. P., Holmes, T. C., & Xu, X.
Affiliations
  • University of California, Irvine (US)
  • Boston University (US)
  • Indiana University Bloomington (US)
Corresponding author
Xu, Xiangmin
ORCID
Venue
Current Biology
Publisher
Elsevier BV
Published
2020-09
Volume
30
Issue
18
Pages
3591-3603.e8
ISSN
0960-9822 (ISSN-L)
DOI
10.1016/j.cub.2020.07.008
PMC
PMC7925140
OpenAlex
W3064508265
Cited by
60
References
13
Citations by year
2026: 7 · 2025: 7 · 2024: 5 · 2023: 12 · 2022: 12 · 2021: 15 · 2020: 2
FWCI
4.70
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Biology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
University of California, Irvine
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Visual perception and processing mechanisms
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
subanesthetic ketamine, amblyopia, neuregulin-1, parvalbumin interneurons, visual cortex, cortical disinhibition, synaptic inhibition, visual acuity recovery, antidepressant mechanism
MeSH terms
Amblyopia, Animals, Female, Ketamine, Male, Neuronal Plasticity, Neurons, Parvalbumins, Synapses, Visual Cortex, Excitatory Amino Acid Antagonists, Neuregulin-1, Mice

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