This work will enable us to address an important gap in moving stem cell therapies from the bench to the clinic. Our investigations in adult mice with acquired temporal lobe epilepsy examine whether transplants of a major inhibitory cell in the brain, the GABAergic interneuron, can suppress seizures by repairing dysfunctional neural circuits in the hippocampus. Following transplantation of stem cell-derived GABAergic interneurons into the dentate gyrus, we will use optogenetics to study whether the transplanted cells suppress spontaneous seizures and prevent axonal sprouting by making strong inhibitory synapses onto newborn hyperexcitable granule neurons.
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