Altered motor coordination, vocal communication, and cerebellar circuit connectivity in mice carrying a near-complete human chromosome 21.

ABSTRACT: Individuals with Down syndrome (DS) frequently face challenges with motor control and coordination, affecting their daily physical movements. The neural mechanism underlying motor coordination deficits in DS remains poorly understood. Using the TcMAC21 mice, which carry an extra nearly complete human chromosome 21 in addition to two copies of mouse orthologs, we characterized altered motor function and identified cerebellar circuit dysfunction underlying motor adaptation deficits. We also revealed disrupted Purkinje neuron organization and hypertrophied synapses from climbing fiber afferents, accompanied by specific deficits in cerebellar-dependent behaviors, including motor learning, vocalizations, and maternal care. In vivo calcium recordings showed stochastic decoupling of cerebellar nu

SUBMITTER: Stander R 

PROVIDER: S-EPMC12789671 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature