Initiation of network bursts by Ca2+-dependent intrinsic bursting in the rat pilocarpine model of temporal lobe epilepsy

1. Chronically epileptic rats, produced by prior injection of pilocarpine, were used to investigate whether changes in intrinsic neuronal excitability may contribute to the epileptogenicity of the hippocampus in experimental temporal lobe epilepsy (TLE). 2. Paired extra-/intracellular electrophysiological recordings were made in the CA1 pyramidal laver in acute hippocampal slices prepared from control and epileptic rats and perfused with artificial cerebrospinal fluid (ACSF). Whereas orthodromic activation of Cd1 neurons evoked only a single, stimul us-graded population spike in control slices, it produced an all-or-none bu rst of population spikes in epileptic: slices. 3. The intrinsic firing patterns of CA1 pyramidal cells were determined by intrasomatic positive current injection. In control slices. the vast majori ty (97%) of the neurons were regular firing cells. In epileptic slices, onl y 53% the pyramidal cells fired in a regular mode. The remaining 47% of the pyramidal cells were intrinsic bursters. These neurons generated high-freq uency bursts of three to six spikes in response to threshold depolarization s. A subgroup of these neurons(10.1% of all cells) also burst fired spontan eously even after suppression of synaptic activity. 4. In epileptic slices, hurst firing in most cases (ca 70%) was completely blocked by adding the Ca2+ channel blocker Ni2+(1 mM) to, or removing Ca2from, the ACSF, but not by intracellular application of the Ca2+ chelater 1 ,2-bis(o-aminophenoxy)ethane-N, N, N ', N ' -tetra-acetic acid (BAPTA), sug gesting it was driven by a Ca2+ current. 5. Spontaneously recurring population bursts were observed in a subset of e pileptic slices. They were abolished by adding 2 muM 6-cyano-7-nitro-quinox aline-2,3-dione (CNQX) to the ACSF, indicating that synaptic excitation is critical for the generation of these events. 6. All sampled pyramidal cells fired repetitively during each population bu rst. The firing of spontaneously active burster's anteceded tile population discharge, whereas: most other pyramidal cells began to fire conjointly wi th the first population spike. Thus, spontaneous bursters are likely to be the initiators of spontaneous population bursts in epileptic slices. 7. The dramatic up-regulation of intrinsic bursting in CA1 pyramidal cells, particularly the dp novo appearance of Ca2+-dependent bursting, may contri bute to the epileptogenicity of the hippocampus in the pilocarpine model of TLE. These findings have important implications for the pharmacological tr eatment of medically refractory human TLE.