Abstract
To find general principles in the cellular mechanisms of epileptogenesis, one must analyze experimental epilepsy models and determine what exists in common between them. We consider here afterdischarges in hippocampal slices induced using either (1) GABAA blockade (e.g. with bicuculline), (2) a bathing solution lacking Mg2+ ions (low Mg-induced epilepsy), or (3) 4-aminopyridine (4AP). By 'afterdischarge' we mean an event that lasts hundreds of milliseconds or more, involving the synchronous firing of all the neurons in a population, shaped into a long initial burst and a series of one or more secondary bursts, and terminating in a prolonged afterhyperpolarization (AHP). We propose that the following features exists in common between these three experimental epilepsies: (1) recurrent excitatory synaptic connections; (2) sustained dendritic synaptic excitation, mediated by either AMPA or NMDA receptors, or both; (3) an intrinsic cellular response to sustained excitation, consisting of rhythmical dendritic bursts, primarily mediated by Ca spikes. In conclusion, if the picture outlined here proves correct, then the stereotypic appearance of epileptic afterdischarges--consisting of synchronized population bursts in series, whatever the network alteration leading to seizures--does indeed reflect a common set of mechanisms. The mechanisms cannot, apparently, be formulated in simple terms of this receptor or that receptor. Rather, we suggest, the recurrent excitatory synapses are able, under diverse circumstances, collectively to produce sustained dendritic conductances in neuronal populations. Pyramidal neurons, by virtue of their normal intrinsic membrane properties, respond to such sustained conductances with rhythmical bursts. The recurrent synapses, in a dual role, serve to maintain the synchrony of these bursts, and so shape the activity into a synchronized oscillation.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.