Structural basis for the role of inhibition in facilitating adult brain plasticity

Chen, Jerry L; Lin, Walter C; Cha, Jae Won; So, Peter T; Kubota, Yoshiyuki; Nedivi, Elly

doi:10.1038/nn.2799

Cited by 214Neuroscience and Neuropharmacology ResearchNeurogenesis and neuroplasticity mechanismsNeural dynamics and brain function

Structural basis for the role of inhibition in facilitating adult brain plasticity

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Chen, Jerry L, Lin, Walter C, Cha, Jae Won, So, Peter T, Kubota, Yoshiyuki, Nedivi, Elly·2011·Nature Neuroscience

DOI 10.1038/nn.2799PMC PMC3083474

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Abstract

Although inhibition has been implicated in mediating plasticity in the adult brain, the underlying mechanism remains unclear. Here we present a structural mechanism for the role of inhibition in experience-dependent plasticity. Using chronic in vivo two-photon microscopy in the mouse neocortex, we show that experience drives structural remodeling of superficial layer 2/3 interneurons in an input- and circuit-specific manner, with up to 16% of branch tips undergoing remodeling. Visual deprivation initially induces dendritic branch retractions, and this is accompanied by a loss of inhibitory inputs onto neighboring pyramidal cells. The resulting decrease in inhibitory tone, also achievable pharmacologically using the antidepressant fluoxetine, provides a permissive environment for further structural adaptation, including addition of new synapse-bearing branch tips. Our findings suggest that therapeutic approaches that reduce inhibition, when combined with an instructive stimulus, could facilitate restructuring of mature circuits impaired by damage or disease, improving function and perhaps enhancing cognitive abilities.

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Fluoxetine activates iPlasticity in adult rat visual cortex in a way that closely resembles the natural critical period and the effects of ChABC or an enriched environment.
“recent findings have shown that the antidepressant fluoxetine activates iPlasticity in the adult rat visual cortex in a manner very similar to that found at the peak of the natural critical period and to that produced by ChABC or enriched environment5,104,141.”
From Neuronal plasticity and neurotrophic factors in drug responses (2017) · cites this paper as [141]
Fluoxetine increases structural plasticity in mouse visual cortex and promotes turnover of synaptic sites.
“Fluoxetine has also been shown to produce enhanced structural plasticity in the mouse visual cortex, promoting turnover of synaptic sites141.”
From Neuronal plasticity and neurotrophic factors in drug responses (2017) · cites this paper as [141]

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Authors: Chen, J. L., Lin, W. C., Cha, J. W., So, P. T., Kubota, Y., & Nedivi, E.
Affiliations: Massachusetts Institute of Technology (US)
Harvard University (US)
The Graduate University for Advanced Studies, SOKENDAI (JP)
Corresponding author: Nedivi, Elly
ORCID: Chen, Jerry L
Cha, Jae Won
So, Peter T
Kubota, Yoshiyuki
Nedivi, Elly
Venue: Nature Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2011-04-10
Volume: 14
Issue: 5
Pages: 587-594
ISSN: 1097-6256 (ISSN-L)
1546-1726
DOI: 10.1038/nn.2799
PMC: PMC3083474
OpenAlex: W2024880767
Cited by: 214
References: 50
Citations by year: 2026: 3 · 2025: 5 · 2024: 7 · 2023: 9 · 2022: 13 · 2021: 13 · 2020: 16 · 2019: 7 · 2018: 13 · 2017: 17 · 2016: 18 · 2015: 22 · 2014: 16 · 2013: 25 · 2012: 20
FWCI: 9.27
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Nature Neuroscience (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
PMC
Funders: Ministry of Education, Culture, Sports, Science and Technology
Stanley Center for Psychiatric Research, Broad Institute
Japan Society for the Promotion of Science
National Eye Institute (R01EY017656)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Keywords: inhibition, adult brain plasticity, visual deprivation, experience-dependent plasticity, pyramidal neurons, inhibitory tone, fluoxetine, synaptogenesis, neocortex, circuit reorganization
MeSH terms: Animals, Dendrites, Fluorescent Dyes, Fluoxetine, Gene Expression Regulation, Interneurons, Functional Laterality, Mice, Transgenic, Models, Biological, Neural Inhibition, Neuronal Plasticity, Sensory Deprivation, Synapses, Time Factors, Visual Pathways, Nonlinear Dynamics, Antidepressive Agents, Second-Generation, Statistics, Nonparametric, Thy-1 Antigens, Neocortex, Green Fluorescent Proteins, Vesicular Inhibitory Amino Acid Transport Proteins, Vesicular Glutamate Transport Protein 1, Mice

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