Assessment of inhibition and epileptiform activity in the septal dentate gyrus of freely behaving rats during the first week after kainate treatment

Mossy fiber reorganization has been hypothesized to restore inhibition mont hs after kainate-induced status epilepticus. The time course of recovery of inhibition after kainate treatment, however, is not well established. We t ested the hypothesis that if inhibition is decreased after kainate treatmen t, it is restored within the first week when little or no mossy fiber reorg anization has occurred. Chronic in vivo recordings of the septal dentate gy rus were performed in rats before and 1, 4, and 7-8 d after kainate (multip le injections of 5 mg/kg, i.p.; n = 17) or saline (n = 11) treatment. Singl e and paired-pulse stimuli were used to assess synaptic inhibition. The fir st day after kainate treatment, only a fraction of rats showed multiple pop ulation spikes (35%), prolonged field postsynaptic potentials (76%), and lo ss of paired-pulse inhibition (29%) to perforant path stimulation. Thus, in hibition was reduced in only some of the kainate-treated rats. By 7-8 d aft er treatment, nearly all kainate-treated rats showed partial or full recove ry in these response characteristics. Histological analysis indicated that kainate-treated rats had a significant decrease in the number of hilar neur ons compared to controls, but Timm staining showed little to no mossy fiber reorganization. These results suggest that a decrease in synaptic inhibiti on in the septal dentate gyrus is not a prerequisite for epileptogenesis an d that most of the recovery of inhibition occurs before robust Timm stainin g in the inner molecular layer.