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J Neurophysiol 96: 2564-2577, 2006. First published July 26, 2006; doi:10.1152/jn.00446.2006
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Role of Persistent Sodium Current in Bursting Activity of Mouse Neocortical Networks In Vitro

Wim van Drongelen1,2, Henner Koch3, Frank P. Elsen1, Hyong C. Lee1, Ana Mrejeru3, Erin Doren1, Charles J. Marcuccilli1, Mark Hereld2,4, Rick L. Stevens2,4 and Jan-Marino Ramirez3

1Department of Pediatrics, 2Computation Institute, and 3Department of Anatomy and Organismal Biology, The University of Chicago, Chicago; and 4Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, Illinois

Submitted 28 April 2006; accepted in final form 20 July 2006

Most types of electrographic epileptiform activity can be characterized by isolated or repetitive bursts in brain electrical activity. This observation is our motivation to determine mechanisms that underlie bursting behavior of neuronal networks. Here we show that the persistent sodium (NaP) current in mouse neocortical slices is associated with cellular bursting and our data suggest that these cells are capable of driving networks into a bursting state. This conclusion is supported by the following observations. 1) Both low concentrations of tetrodotoxin (TTX) and riluzole reduce and eventually stop network bursting while they simultaneously abolish intrinsic bursting properties and sensitivity levels to electrical stimulation in individual intrinsically bursting cells. 2) The sensitivity levels of regular spiking neurons are not significantly affected by riluzole or TTX at the termination of network bursting. 3) Propagation of cellular bursting in a neuronal network depended on excitatory connectivity and disappeared on bath application of CNQX (20 µM) + CPP (10 µM). 4) Voltage-clamp measurements show that riluzole (20 µM) and very low concentrations of TTX (50 nM) attenuate NaP currents in the neural membrane within a 1-min interval after bath application of the drug. 5) Recordings of synaptic activity demonstrate that riluzole at this concentration does not affect synaptic properties. 6) Simulations with a neocortical network model including different types of pyramidal cells, inhibitory interneurons, neurons with and without NaP currents, and recurrent excitation confirm the essence of our experimental observations that NaP conductance can be a critical factor sustaining slow population bursting.


Address for reprint requests and other correspondence: W. van Drongelen, Department of Pediatrics, C372, MC 3055, 5841 S. Maryland Ave., Chicago, IL 60637-1470 (E-mail: wvandron{at}peds.bsd.uchicago.edu)




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