Long term repair of learning disability through short-term reduction of CNS inhibition

Learning disabilities are serious societal problems contributing to a loss of quality of life for affected individuals and their families. We hypothesized that the learning disability in Down Syndrome and perhaps in other neurodegenerative disorders is due to an imbalance between inhibitory and excitatory tone in the CNS. Specifically, we predicted that reduction of GABA related inhibition would improve learning. We used the TsDn65 mouse model of Down Syndrome and treated adult mice with daily doses of different GABA antagonists. Following treatments learning performance of these mice in several rodent learning tasks was indistinguishable from the performance of wild type mice, and the learning improvement lasted for months after the treatment ended. We are now exploring the mechanism of this durable neuroplastic effect and asking whether it would generalize to other learning disorders or optimize learning in wild type mice.