TY - JOUR T1 - Motor training improves coordination and anxiety in symptomatic <em>Mecp2</em>-null mice despite impaired functional connectivity within the motor circuit JF - bioRxiv DO - 10.1101/786822 SP - 786822 AU - Yuanlei Yue AU - Pan Xu AU - Zhichao Liu AU - Xiaoqian Sun AU - Juntao Su AU - Hongfei Du AU - Lingling Chen AU - Ryan T. Ash AU - Stelios Smirnakis AU - Rahul Simha AU - Linda Kusner AU - Chen Zeng AU - Hui Lu Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/08/11/786822.abstract N2 - 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. ER -