GABA progenitors grafted into the adult epileptic brain control seizures and abnormal behavior

Impaired GABA–mediated neurotransmission has been implicated in many neurologic diseases including epilepsy, intellectual disability, and psychiatric disorders. Here we report that inhibitory neuron transplantation into the hippocampus of adult mice with confirmed epilepsy at the time of grafting dramatically reduced the occurrence of electrographic seizures and restored behavioral deficits in spatial learning, hyperactivity, and the aggressive response to handling. In the recipient brain, GABA progenitors migrated up to 1500 μm from the injection site, expressed genes and proteins characteristic for interneurons, differentiated into functional inhibitory neurons, and received excitatory synaptic input. In contrast to hippocampus, cell grafts into basolateral amygdala rescued the hyperactivity deficit but did not alter seizure activity or other abnormal behaviors. Our results highlight a critical role for interneurons in epilepsy and suggest that interneuron cell transplantation is a powerful approach to halt seizures and rescue accompanying deficits in severely epileptic mice.