Motor training improves coordination and anxiety in symptomatic Mecp2 -null mice despite impaired functional connectivity within the motor circuit.

Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101653440 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2375-2548 (Electronic) Linking ISSN: 23752548 NLM ISO Abbreviation: Sci Adv Subsets: PubMed not MEDLINE; MEDLINE

Original Publication: Washington, DC : American Association for the Advancement of Science, [2015]-

Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by loss of function of the X-linked methyl-CpG–binding protein 2 ( MECP2 ). Several case studies report that gross motor function can be improved in children with RTT through treadmill walking, but whether the MeCP2-deficient motor circuit can support actual motor learning remains unclear. We used two-photon calcium imaging to simultaneously observe layer (L) 2/3 and L5a excitatory neuronal activity in the motor cortex (M1) while mice adapted to changing speeds on a computerized running wheel. Despite circuit hypoactivity and weakened functional connectivity across L2/3 and L5a, the Mecp2 -null circuit’s firing pattern evolved with improved performance over 2 weeks. Moreover, trained mice became less anxious and lived 20% longer than untrained mice. Because motor deficits and anxiety are core symptoms of RTT, which is not diagnosed until well after symptom onset, these results underscore the benefit of motor learning.

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R00 NS089824 United States NS NINDS NIH HHS; R21 NS096640 United States NS NINDS NIH HHS

Date Created: 20211022 Latest Revision: 20240923

20240923

PMC8535852

10.1126/sciadv.abf7467

34678068