This Project Grant award from the National Institutes of Health (CFDA 93.310 Trans-NIH Research Support) provides $2,357,335 to Trustees of Boston University, doing business as Boston University Medical Campus, to study neuronal dysfunction in Down syndrome and develop advanced in vitro and in vivo models. Key objectives include:
Utilizing cortical organoids and assembloids (fusion of dorsal and ventral organoids) to examine the cellular, transcriptomic, and functional changes driven by Down syndrome trisomy. The researchers will assess neuronal activity, connectivity, and migration of inhibitory interneurons using electrophysiology, calcium imaging, and histological methods.
Xenotransplanting the cortical organoids into the retrosplenial cortex of immunodeficient mice to monitor the development of spontaneous and stimulus-triggered neuronal activity, cellular integration with the host brain, and Down syndrome-related Alzheimer's disease pathology. This in vivo model leverages transparent graphene microelectrode arrays for longitudinal functional assessments.
Additionally, the award includes a $127,460 sub-grant to UC San Diego to support the fabrication of transparent microelectrode arrays for use in the neuronal activity studies on the cortical organoids.
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