Cellular/Molecular Decrease in Tonic Inhibition Contributes to Increase in

Brain injury is an etiological factor for temporal lobe epilepsy and can lead tomemory and cognitive impairments. A recently character-ized excitatoryneuronal class in thedentatemolecular layer, semilunar granule cell (SGC), hasbeenproposed to regulatedentatenetwork activity patterns and working memory formation. Although SGCs, like granule cells, project to CA3, their typical sustained firing and associational axon collaterals suggest that they are functionally distinct from granule cells. We find that brain injury results in an enhancement of SGC excitability associatedwith an increase in input resistance 1week after trauma. In addition to prolongingminiature and spontaneous IPSC interevent intervals, brain injury significantly reduces the amplitude of tonic GABA currents in SGCs. The postinjury decrease in SGC tonic GABA currents is in direct contrast to the increase observed in granule cells after trauma. Although our observation that SGCs express Prox1 indicates a shared lineage with granule cells, data from control rats show that SGC tonic GABA currents are larger and sIPSC interevent intervals shorter than in granule cells, demonstrating inherent differences in inhibition between these cell types. GABAA receptor antagonists selectively augmented SGC input resistance in controls but not in head-injured rats. Moreover, post-traumatic differences in SGC firing were abolished in GABAA receptor blockers. Our data show that cell-type-specific post-traumatic decreases in tonic GABA currents boost SGC excitability after brain injury. Hyperexcitable SGCs could augment dentate throughput to CA3 and contribute substantively to the enhanced risk for epilepsy andmemory dysfunction after traumatic brain injury