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Brief "inlerictal" epileptic events in the hippocampus and other cortical regions result from the excitatory synaptic network between pyramidal cells. A comhi-nation of experiments, mainly on slices in vitro, and realistic computer simulations has shown how excitatory networks can recruit the whole population of pyramidal cells into a hypersynchronous epileptic discharge. While the details vary, the same general principles apply to a range of experimental models including picrotoxin, bicuculline, 4-aminopyridine. Iow-Mg2+ and high K+. The necessary features of the network are that: the excitatory connections are divergent, excitatory synapses are effective in exciting their targets, and the population is above a minimum critical size (Traub & Jefferys, pp 405-18 in: Epilepsy: A Comprehensive Textbook, eds Engel & Pedley, 1997). This scheme is effective in explaining events last 100-200 ms, and can be extended to events lasting up to 0.5s (resembling EEC polyspikes). Events lasting as long a seizure require something extra. Hippocampal slices produce several distinct kinds of "seizure-like events". I will discuss two broad classes here. The first, seen under bicuculline, arises in the CA3 region of ventral hippocampal slices in the presence of slightly elevated K+ (5 mM), as long as the dentate hilus is present. Epileptic activity then can propagate to CA1, the entorhinal cortex, and also to the dentate gyrus (C Borck). These discharges comprise 3 distinct phases. The primary discharge last 100-200 ms and resembles interjetai bursts. Secondary bursts: ride on the same pyramidal cell depolarisation as the primary, extend the discharge to 400 ms, occur at 15-30 Hz, and are the only component sensitive to NMDA receptor antagonists. Tertiary bursts represent the hulk of the seizure like event. They arise from close to resting potential, and are associated with substantial increases in spontaneous synaptic activity. They occur when [K+]0 reaches over 8.5 mM during the primary burst. We hypothesize that the elevated [K+]o promotes spontaneous ectopic spikes and/or transmitter release, providing an increase in excitatory tone which accelerates discharges, resembling the primary burst, into a train at 0.5-7 Hz, lasting up to 90 s. The second class of seizure-like event arises in the CA1 region. Non-synaptic mechanisms make a much greater contribution. In some cases, such as in the high-K+ model, they closely resemble "field bursts" first identified in nominally Ca2+-free solutions during the early 1980's. Increased [K+]0 makes CA1 neurons hyperexcitable, and electric field effects synchronize action potentials in different neurons on a ms time scale. We recently identified a variation on this theme in the low-Mg2+ and 4-aminopyridine models (R Kohling and H Station, respectively). Brief interjetai bursts in CA3 trigger a rhythmic discharge resembling tetanically-evoked gamma rhythms, which can last for many seconds, and which can trigger further epileptic bursts in CA1. The CA1 discharge is due to be a slow depolarisation which results from prolonged GABAA receptor activity, both direclly through depolarising shifts in GABAA receptor reversal potential, and indirectly through accumulation of [K+]o The discharges of the CA1 neuronal population are again synchronised on a ms time scale to produce large population spikes. A key question is whether these processes occur in vivo. We have studied chronic epileptic foci induced by intrahippocampal tetanus toxin. The spontaneous seizures in this model do not have components that obviously resemble the second (CA1-dependent) class of seizure-like activity (GT Finnerty). They do have components similar to the primary, secondary and "tertiary" (here ∼10 Hz) bursts generated by CA3, although they are separated by other kinds of discharge which are not (so far) replicated in slices, and which may depend on more extensive network interactions.


Journal article


Italian Journal of Neurological Sciences

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