title: Decrease in tonic inhibition contributes to increase in dentate semilunar granule cell excitability after brain injury.
abstract: Brain injury is an etiological factor for temporal lobe epilepsy and can lead to memory and cognitive impairments. A recently characterized excitatory neuronal class in the dentate molecular layer, semilunar granule cell (SGC), has been proposed to regulate dentate network 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 associated with an increase in input resistance 1 week after trauma. In addition to prolonging miniature 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. GABA(A) 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 GABA(A) 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 and memory dysfunction after traumatic brain injury.
authors.affiliation: Department of Neurology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103, USA.
authors.forename: Akshay
authors.initials: A
authors.lastname: Gupta
authors.forename: Fatima S
authors.initials: FS
authors.lastname: Elgammal
authors.forename: Archana
authors.initials: A
authors.lastname: Proddutur
authors.forename: Samik
authors.initials: S
authors.lastname: Shah
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Santhakumar
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology*; D018891:Dentate Gyrus / Q000166:cytology* / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000502:physiology