Inhibition modifies the effects of slow calcium-activated potassium channels on epileptiform activity in a neuronal network model

• Published in: Biological cybernetics 2005-02, Vol.92 (2), p.71-81
• Main Authors: Yang, K-H, Franaszczuk, Piotr J, Bergey, Gregory K
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Animals; Bursting; Delay; Excitation; Feedback; gamma-Aminobutyric Acid - pharmacology; Inhibition; Membranes; Models, Neurological; Modulators; Networks; Neural Conduction - drug effects; Neural Conduction - physiology; Neural Inhibition - drug effects; Neural Inhibition - physiology; Neural Networks (Computer); Neurons; Potassium Channels, Calcium-Activated - drug effects; Potassium Channels, Calcium-Activated - physiology; Pyramidal Cells - drug effects; Pyramidal Cells - physiology; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Time Factors
• ISSN: 0340-1200; 1432-0770
• DOI: 10.1007/s00422-004-0532-0

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 Ca(2+)-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.