Document Type

Article

Publication Date

2005

Abstract

Generation of epileptiform activity typically results from a change in the balance between network excitation and inhibition. Experimental evidence indicates that alterations of either synaptic activity or intrinsic membrane properties can produce increased network excitation. The slow Ca2+-activated K+ currents (sI AHP) are important modulators of neuronal firing rate and excitability and have important established and potential roles in epileptogenesis. While the effects of changes in sI AHP on individual neuronal excitability are readily studied and well established, the effects of such changes on network behavior are less well known. The experiments here utilize a defined small network model of multicompartment pyramidal cells and an inhibitory interneuron to study the effects of changes in sI AHP on network behavior. The benefits of this model system include the ability to observe activity in all cells in a network and the effects of interactions of multiple simultaneous influences. In the model with no inhibitory interneuron, increasing sI AHP results in progressively decreasing burst activity. Adding an inhibitory interneuron changes the observed effects; at modest inhibitory strengths, increasing sI AHP in all network neurons actually results in increased network bursting (except at very high values). The duration of the burst activity is influenced by the length of delay in a feedback loop, with longer loops resulting in more prolonged bursting. These observations illustrate that the study of potential antiepileptogenic membrane effects must be extended to realistic networks. Network inhibition can dramatically alter the observations seen in pure excitatory networks.

Comments

This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Biological Cybernetics, volume 92, issue 2, 2005 following peer review. The final publication is available at Springer via DOI: 10.1007/s00422-004-0532-0.

Peer Reviewed

1

Copyright

Springer

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