Reduction in focal ictal activity following transplantation of MGE interneurons requires expression of the GABAA receptor α4 subunit.

摘要: Despite numerous advances, treatment-resistant seizures remain an important problem. Loss of neuronal inhibition is present in a variety epilepsy models and suggested as mechanism for increased excitability, leading to the proposal that grafting inhibitory interneurons into seizure foci might relieve refractory seizures. Indeed, transplanted medial ganglionic eminence interneuron progenitors (MGE-IPs) mature GABAergic increase GABA release onto cortical pyramidal neurons, this associated with reduced activity. An obvious conclusion coupling between new cells underlies effect. We hypothesized primary seizure-limiting effects following MGE-IP transplantation tonic conductance results from activation extrasynaptic GABAA receptors (GABAA-Rs) expressed on cells. Using vitro vivo recording techniques, we demonstrate GABAA-R α4 subunit deletion abolishes currents (Itonic) leads failure attenuate propagation. These observations should influence how field proceeds respect further development therapeutic transplants (and possibly pharmacological treatments).