The right cells, the right place, the right result: transplants to alleviate seizures take a step forward.

Commentary Synaptic inhibition critically controls neural circuit excitabil-ity in the brain; reduced functional inhibition due to loss of GABAergic neurons, dysregulation of surviving GABA cells, and altered GABA receptor responses accompanies development of spontaneous seizures in animal models of acquired temporal lobe epilepsy (TLE). In many TLE patients, altered inhibitory control is also implied by the success of anti-seizure therapy with drugs that potentiate GABA's effects in the brain. Systemic drug treatment, however, affects circuits throughout the brain—not just in seizure-producing areas—sometimes leading to unwanted side effects. Further, epilepsy symptoms are pharmacologically refractory in a significant percentage of TLE patients. Hunt and colleagues explored the attractive proposition that reinstatement of constitutive GABA function in specific neural circuitry affected by seizures might offer a novel avenue for treating seizures using medial ganglionic eminence (MGE) progenitor cells, transplanted into the hip-pocampus in a mouse model of acquired TLE in adults. The pilocarpine-treated mouse model used here is a robust model of adult onset acquired epilepsy in rodents. It shares many cellular and behavioral features with TLE patients, including loss of inhibitory interneurons, axon sprouting, synaptic reorganization, memory and anxiety irregularities, and frequent spontaneous seizures that are often pharma-coresistant. The present study transplanted MGE progenitor cells (undifferentiated, post-mitotic cells destined primarily to become GABAergic interneurons) into the hippocampi of adult mice with established epilepsy (i.e., they displayed spontaneous seizures). They found that transplanted MGE cells developed mainly into GABA neurons, as expected, and integrated into hippocampal synaptic circuitry. Concurrently, transplant recipients experienced a greater than 90% reduction in seizure frequency and restoration of several epilepsy-related behav-ioral deficits. Obligatory scientific caveats aside, it is tantalizing to speculate that the transplanted MGE-derived GABA neurons functionally replaced those cells lost in the initial insult (i.e., status epilepticus) used to trigger the development of TLE in these mice. The successful functional integration of GABAergic interneuron progenitors in an adult model of TLE appears to represent a significant step in developing new anti-epileptic treatments. Successful integration of undifferentiated, embryonic stem (ES) cell progenitors transplanted into adult hippocampal circuits was demonstrated recently in the pilocarpine-treated mouse, but functional outcomes on seizures were not addressed , and many ES cell-derived neurons differentiated into non-GABAergic phenotypes (1). Adding to previous findings from immature mice by the Baraban group using a genetic epilepsy model (2), the work described by Hunt et al. significantly advances previous understanding of neural transplantation for epilepsy treatment …