RT Journal Article SR Electronic T1 Motor training improves coordination and anxiety in symptomatic Mecp2-null mice despite impaired functional connectivity within the motor circuit JF bioRxiv FD Cold Spring Harbor Laboratory SP 786822 DO 10.1101/786822 A1 Yuanlei Yue A1 Pan Xu A1 Zhichao Liu A1 Xiaoqian Sun A1 Juntao Su A1 Hongfei Du A1 Lingling Chen A1 Ryan T. Ash A1 Stelios Smirnakis A1 Rahul Simha A1 Linda Kusner A1 Chen Zeng A1 Hui Lu YR 2021 UL http://biorxiv.org/content/early/2021/08/11/786822.abstract AB 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 two weeks. Moreover, trained mice became less anxious and lived 20% longer than untrained mice. Since motor deficits and anxiety are core symptoms of Rett, which is not diagnosed until well after symptom onset, these results underscore the benefit of motor learning.Competing Interest StatementThe authors have declared no competing interest.