Abstracts

Rationale: Development of epilepsy following unprovoked seizures is characterized by cell-type specific changes in neuronal excitability, inhibition, and connectivity in the dentate gyrus. Perisomatically projecting GABAergic neurons in the hilar-granule cell layer border, known as fast-spiking basket cells (FS-BCs), show sustained high-frequency firing, express parvalbumin, and are critical in maintaining the low excitability of granule cells. Earlier studies have suggested that parvalbumin-positive basket cells are less susceptible to seizure-induced cell loss compared to other interneurons. Therefore, changes in FS-BC excitability and inhibition will heavily impact the function of dentate networks following seizures. However, whether GABAergic inhibition of FS-BCs is altered following seizures is not known. Interestingly, although hilar-granule cell layer border neurons express GABAa receptor subunits that underlie tonic inhibition, the identity of this interneuronal population is also not known. Since altered FS-BC inhibition could influence dentate excitability, synchrony, and epileptogenicity, we examined FS-BCs for the presence and seizure-induced changes in tonic GABA currents.Methods: Immunohistochemical studies and patch-clamp experiments were conducted in hippocampal slices from male rats obtained 1 week and > 30 days after pilocarpine induced status epilepticus (SE) and in saline-injected controls.Results: Immunostaining identified that a population of neurons expressing the GABAa receptor ? subunits in the hilar-granule cell layer border was immunoreactive for parvalbumin. The GABAa receptor antagonist bicuculline (BMI, 100 ?M) decreased the baseline holding currents in morphologically and physiologically identified FS-BCs indicating the presence of tonic GABA currents (tonic GABA currents: 7.0 3.1 pA, n=9 cells). However, in non fast-spiking hilar interneurons, the change in baseline currents in BMI was not statistically significant (tonic GABA currents: 1.0 1.2 pA, n=9 cells). Tonic GABA currents in FS-BCs recorded in the GABA transporter antagonist, NO-711 (10 ?M), were increased after SE (in pA, CON: 14. 7 2.6, n=6; post-SE: 25.9 3.1, n=5, p<0.05). FS-BC tonic GABA currents were enhanced by THIP (1 ?M) in both control and post-SE rats indicating the contribution of GABAa receptors with ? subunits. Gramicidin perforated-patch recordings revealed that, compared to controls, the reversal potential of GABA evoked currents was depolarized in hilar-granule cell layer border interneurons from post-SE rats (in mV, CON: -71.86 5.14, n=5; Post-SE: -56.2 2.88, n=7, p<0.05).Conclusions: These data demonstrate the presence and post-SE enhancement of tonic GABA currents in dentate FS-BCs. Together, enhanced tonic GABA currents and depolarized GABA reversal are likely to alter FS-BC excitability and feed-back inhibition following status epilepticus.