A Dive Into Cerebellar Dysfunction, Motor Deficits and GABAergic Signaling in Down Syndrome

Down syndrome (DS) mouse models and DS human fetus studies clearly indicate severe neurogenesis impairment in the cerebellum. Clinical features of DS include motor dysfunction and cerebellar hypotrophy, with a particularly marked decrease in the number of granule cells (GCs). GCs are crucial for managing sensory communication within the cerebellum via mossy fibers and their interactions with Purkinje cells (PCs) and inhibitory interneurons. The current review discusses cerebellar alterations in DS and its impact on GABAergic transmission, bringing to light the impact on GABAergic signaling and its role in motor coordination dysfunction observed in individuals with DS. The findings highlight the significance of GABAergic transmission in the pathophysiology of DS and its potential as a target for therapeutic innervation. Moreover, understanding the disruptions in GABAergic signaling may provide insights into developing novel treatment strategies.