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1 Pediatrics, The University of Chicago, Chicago, Illinois, United States; Computation Institute, The University of Chicago, Chicago, Illinois, United States
2 Anatomy and Organismal Biology, The University of Chicago, Chicago, Illinois, United States
3 Pediatrics, The University of Chicago, Chicago, Illinois, United States
4 Computation Institute, The University of Chicago, Chicago, Illinois, United States; Mathematics and Computerscience, Argonne National Laboratory, Argonne, Illinois, United States
* To whom correspondence should be addressed. E-mail: wvandron{at}peds.bsd.uchicago.edu.
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 current (NaP) in mouse neocortical slices is associated with cellular bursting, and our data suggests 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 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 upon 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 one-minute 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.
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