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Sensory experience regulates cortical inhibition by inducing IGF1 in VIP neurons
Open accessAbstract
Inhibitory neurons regulate the adaptation of neural circuits to sensory experience, but the molecular mechanisms by which experience controls the connectivity between different types of inhibitory neuron to regulate cortical plasticity are largely unknown. Here we show that exposure of dark-housed mice to light induces a gene program in cortical vasoactive intestinal peptide (VIP)-expressing neurons that is markedly distinct from that induced in excitatory neurons and other subtypes of inhibitory neuron. We identify Igf1 as one of several activity-regulated genes that are specific to VIP neurons, and demonstrate that IGF1 functions cell-autonomously in VIP neurons to increase inhibitory synaptic input onto these neurons. Our findings further suggest that in cortical VIP neurons, experience-dependent gene transcription regulates visual acuity by activating the expression of IGF1, thus promoting the inhibition of disinhibitory neurons and affecting inhibition onto cortical pyramidal neurons.
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“In contrast, neuronal activity induces a completely different transcriptional response in VIP+ interneurons, promoting the formation of inhibitory synapses on these cells (Mardinly et al., 2016).”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Mardinly et al., 2016
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Cites
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Three-dimensional intact-tissue sequencing of single-cell transcriptional states
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“1A and 2, A and B) to survey a large but focused and curated gene set [160 genes including 112 putative cell-type markers collated from mouse cortical single-cell RNA sequencing (24, 25) and 48 activity-regulated genes (ARGs) (26, 27)].”
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“The values shown are absolute number of cells that migrated to the other side (approximately the same area and thickness was imaged in each session); one-way ANOVA for cells at 17 days after assembly; F(2, 32)= 8.”
Development and Functional Diversification of Cortical Interneurons
Lim, L., Mi, D., Llorca, A., & Marín, O. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.009 · Cited by 714
Activity-Regulated Transcription: Bridging the Gap between Neural Activity and Behavior
Yap, E.-L., & Greenberg, M. E. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.013 · Cited by 706
“Many IEGs encode sequence-specific DNA-binding proteins that function as transcription factors (TFs) and regulate a subsequent wave of lateresponse gene (LRG) expression, which is now known to be cell-type specific and tailored to the specific function of the cell within a neural circuit (Mardinly et al., 2016; Sheng…”
BackgroundResultInfluentialSingle-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex
Hrvatin, S., Hochbaum, D. R., Nagy, M. A., Cicconet, M., Robertson, K., Cheadle, L., Zilionis, R., Ratner, A., Borges-Monroy, R., Klein, A. M., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-017-0029-5 · Cited by 497
Self-citation
Metadata
- Authors
- Mardinly, A. R., Spiegel, I., Patrizi, A., Centofante, E., Bazinet, J. E., Tzeng, C. P., Mandel-Brehm, C., Harmin, D. A., Adesnik, H., Fagiolini, M., & Greenberg, M. E.
- Affiliations
- University of California, Berkeley (US)
- Harvard University (US)
- Boston Children's Hospital (US)
- Corresponding author
- Greenberg, M. E.
- ORCID
- Venue
- Nature
- Published
- 2016-03
- Volume
- 531
- Issue
- 7594
- Pages
- 371-375
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4823817
- OpenAlex
- W2293311540
- Cited by
- 176
- References
- 37
- Citations by year
- 2026: 6 · 2025: 22 · 2024: 12 · 2023: 14 · 2022: 18 · 2021: 17 · 2020: 13 · 2019: 23 · 2018: 19 · 2017: 20 · 2016: 12
- FWCI
- 13.83
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (P01NS047572, R01NS028829, R37NS028829)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD018655)
- 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 › Visual perception and processing mechanisms
- Keywords
- insulin-like growth factor I, cortical inhibition, visual cortex, visual acuity, excitation-inhibition balance, light exposure, activity-dependent gene expression, inhibitory synaptic input, cortical plasticity, pyramidal neurons
- MeSH terms
- Animals, Female, Insulin-Like Growth Factor I, Male, Mice, Inbred C57BL, Neural Inhibition, Neural Pathways, Neuronal Plasticity, Neurons, Synapses, Vasoactive Intestinal Peptide, Vision, Ocular, Visual Cortex, Pyramidal Cells, Mice
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