Gallo, Vittorio PHD

This is a new application for the DC-IDDRC, the District of Columbia Intellectual and Developmental Disabilities Research Center. The DC-IDDRC is dedicated to improving the lives of individuals with intellectual and developmental disabilities (IDDs) and their families by creating a strong translational research environment optimized for studying and defining the basic causes and mechanisms underlying IDDs, and designing new effective treatments and prevention strategies. To realize this mission, we provide a rich environment for performing fully translational IDD research in the four collaborating DC academic medical centers (Children’s National Hospital (lead), George Washington University, Howard University, and Georgetown University).

The novel understanding of oligodendrocyte maturation defects in brains of humans with Down syndrome and the Ts65Dn mouse model open a new avenue to possible cognitive therapies for persons with Down syndrome—we have shown that these cellular defects lead to less myelin in the forebrain and cerebellum and that this causes slower neuronal transmission in the brain. The experiments in this proposal are designed to uncover the cell intrinsic and extrinsic mechanisms underlying the cellular defect and to measure whether motor and/or spatial learning and memory are correlated with the dysmyelination. Finally, we will investigate genetic and pharmacological therapies designed to promote myelination and improve cognitive and motor function.

Neural basis of locomotor dysfunction in Down Syndrome PI: Gallo, Vittorio, PhD Down syndrome (DS), the most commonly diagnosed chromosomal condition, affects a range of behavioral domains in children including motor and cognitive function. Cerebellar pathology has been consistently observed in DS, and is thought to contribute to dysfunction in locomotor and adaptive motor skills. However, the specific neural pathways underlying locomotor learning that are disrupted in DS remain poorly understood. The main goal of this proposal is to identify specific alterations in the circuitry of the cerebellum that results in locomotor dysfunction in DS. This will enable precise identification of circuit-to-behavior mechanisms disrupted in DS.