Journal
NATURE NEUROSCIENCE
Volume 24, Issue 5, Pages 646-657Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41593-021-00815-7
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Funding
- Canada Research Chair (CRC) [950-231274]
- Canadian Institutes of Health Research (CIHR) [153254]
- Natural Sciences and Engineering Research Council of Canada (NSERC) [05308]
- Simons Foundation
- Scottish Rite Charitable Foundation
- Brain AMP
- Behavior Research Foundation (NARSAD) [27177]
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The study revealed delayed motor learning in mice with 16p11.2 deletion, associated with abnormal ensemble activity and delayed spine remodeling in the motor cortex. Activation of locus coeruleus noradrenergic neurons rescued the motor-related abnormalities in these mice.
Children with autism spectrum disorder often exhibit delays in achieving motor developmental milestones such as crawling, walking and speech articulation. However, little is known about the neural mechanisms underlying motor-related deficits. Here, we reveal that mice with a syntenic deletion of the chromosome 16p11.2, a common copy number variation associated with autism spectrum disorder, also exhibit delayed motor learning without showing gross motor deficits. Using in vivo two-photon imaging in awake mice, we find that layer 2/3 excitatory neurons in the motor cortex of adult male 16p11.2-deletion mice show abnormally high activity during the initial phase of learning, and the process of learning-induced spine reorganization is prolonged. Pharmacogenetic activation of locus coeruleus noradrenergic neurons was sufficient to rescue the circuit deficits and the delayed motor learning in these mice. Our results unveil an unanticipated role of noradrenergic neuromodulation in improving the delayed motor learning in 16p11.2-deletion male mice. Yin et al. show that motor learning is delayed in mice with 16p11.2 deletion, associated with abnormal ensemble activity and delayed spine remodeling in motor cortex and reduced activity of of locus coeruleus noradrenergic neurons. The motor-related abnormalities were rescued by activation of ocus coeruleus noradrenergic neurons.
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