Sensory experience remodels genome architecture in neural circuit to drive motor learning
Open accessAbstract
Neuronal-activity-dependent transcription couples sensory experience to adaptive responses of the brain including learning and memory. Mechanisms of activity-dependent gene expression including alterations of the epigenome have been characterized 1-8. However, the fundamental question of whether sensory experience remodels chromatin architecture in the adult brain in vivo to induce neural code transformations and learning and memory remains to be addressed. Here we use in vivo calcium imaging, optogenetics and pharmacological approaches to show that granule neuron activation in the anterior dorsal cerebellar vermis has a crucial role in a delay tactile startle learning paradigm in mice. Of note, using large-scale transcriptome and chromatin profiling, we show that activation of the motor-learning-linked granule neuron circuit reorganizes neuronal chromatin including through long-distance enhancer-promoter and transcriptionally active compartment interactions to orchestrate distinct granule neuron gene expression modules. Conditional CRISPR knockout of the chromatin architecture regulator cohesin in anterior dorsal cerebellar vermis granule neurons in adult mice disrupts enhancer-promoter interactions, activity-dependent transcription and motor learning. These findings define how sensory experience patterns chromatin architecture and neural circuit coding in the brain to drive motor learning.
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The 3D genome is actively regulated during learning and memory formation.
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The 3D genome plays an important role in neuronal gene expression and function.
“The 3D genome plays an important role in neuronal gene expression and function”
From Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration (2023) · cites this paper as [36]
The SRG Nr4a3 engages in multiple long-range contacts over several hundred kb after neuronal stimulation.
“Consistent with our observations, another study reported—using H3K4me3 proximity ligation assisted ChIP–seq (PLAC-seq)—that the SRG Nr4a3 engages in multiple long-range contacts over several hundred kb after neuronal stimulation26.”
From Three-dimensional genome restructuring across timescales of activity-induced neuronal gene expression (2020) · cites this paper as [26]
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- Authors
- Yamada, T., Yang, Y., Valnegri, P., Juric, I., Abnousi, A., Markwalter, K. H., Guthrie, A. N., Godec, A., Oldenborg, A., Hu, M., Holy, T. E., & Bonni, A.
- Affiliations
- University of Tsukuba (JP)
- Northwestern University (US)
- Washington University in St. Louis (US)
- Cleveland Clinic (US)
- Corresponding author
- Yamada, Tomoko
- Bonni, Azad
- ORCID
- Venue
- Nature
- Published
- 2019-05
- Volume
- 569
- Issue
- 7758
- Pages
- 708-713
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6542709
- OpenAlex
- W2944536114
- Cited by
- 83
- References
- 47
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 11 · 2023: 7 · 2022: 16 · 2021: 14 · 2020: 6 · 2019: 10
- FWCI
- 3.78
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-05-22)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (U54DK107977)
- National Institute of Neurological Disorders and Stroke (R01NS041021, UF1NS108176)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- sensory experience, chromatin structure, motor learning, cerebellar vermis, granule neurons, enhancer-promoter interactions, cohesin, activity-dependent transcription, epigenetic regulation, gene modules
- MeSH terms
- Animals, DNA-Binding Proteins, Enhancer Elements, Genetic, Female, Learning, Male, Motor Skills, Neural Pathways, Neuronal Plasticity, Promoter Regions, Genetic, Purkinje Cells, Reflex, Startle, Genome, Cell Cycle Proteins, Mossy Fibers, Hippocampal, Chromatin Assembly and Disassembly, Epigenesis, Genetic, Mice, Feedback, Sensory, Cerebellar Vermis
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