Short- and long-term changes in CA1 network excitability after kainate treatment in rats

Neuron loss, axon sprouting, and the formation of new synaptic circuits hav e been hypothesized to contribute to seizures in temporal lobe epilepsy (TL E). Using the kainate-treated rat, we examined how alterations in the densi ty of CA1 pyramidal cells and interneurons, and subsequent sprouting of CA1 pyramidal cell axons, were temporally associated with functional changes i n the network properties of the CA1 area. Control rats were compared with a nimals during the first week after kainate treatment versus several weeks a fter treatment. The density of CA1 pyramidal cells and putative inhibitory neurons in stratum oriens was reduced within 8 days after kainate treatment . Axon branching of CA1 pyramidal cells was similar between controls and an imals examined in the first week after kainate treatment but was increased several weeks after kainate treatment. Stimulation of afferent fibers in br ain slices containing the isolated CA1 region produced graded responses in slices from controls and kainate-treated rats tested,8 days after treatment . In contrast, synchronous all-or-none bursts of spikes at low stimulus int ensity (i.e., "network bursts") were only observed in the CA1 several weeks after kainate treatment. In the presence of bicuculline, the duration of e voked bursts was significantly longer in CA1 pyramidal cells weeks after ka inate treatment than from controls or those examined in the first week post treatment. Spontaneous network bursts were also observed in the isolated CA 1 several weeks after kainate treatment in bicuculline-treated slices. The data suggest that the early loss of neurons directly associated with kainat e-induced status epilepticus is followed by increased axon sprouting and ne w recurrent excitatory circuits in CA1 pyramidal cells. These changes chara cterize the transition from the initial acute effects of the kainate-induce d insult to the eventual development of all-or-none epileptiform discharges in the CA1 area.