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Sensory experience remodels genome architecture in neural circuit to drive motor learning

ABSTRACT: 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. However, the fundamental question of whether and how 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, in vivo calcium imaging, optogenetics, and pharmacological approaches reveal that granule neuron activation in the anterior dorsal cerebellar vermis (ADCV) plays a crucial role in a novel delay tactile startle learning paradigm in mice. Strikingly, using large-scale transcriptome and chromatin profiling, we have discovered 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 ADCV granule neurons in adult mice disrupts 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE127995 | GEO | 2019/05/09

REPOSITORIES: GEO

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Sensory experience remodels genome architecture in neural circuit to drive motor learning

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