Faculty Collaboration Database

Role of persistent sodium current in bursting activity of mouse neocortical networks in vitro. J Neurophysiol 2006 Nov;96(5):2564-77

Date

07/28/2006

Pubmed ID

16870839

DOI

10.1152/jn.00446.2006

Scopus ID

2-s2.0-84983719395 (requires institutional sign-in at Scopus site)   54 Citations

Abstract

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 (Na(P)) 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 microM) + CPP (10 microM). 4) Voltage-clamp measurements show that riluzole (20 microM) and very low concentrations of TTX (50 nM) attenuate Na(P) 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 Na(P) currents, and recurrent excitation confirm the essence of our experimental observations that Na(P) conductance can be a critical factor sustaining slow population bursting.

Author List

van Drongelen W, Koch H, Elsen FP, Lee HC, Mrejeru A, Doren E, Marcuccilli CJ, Hereld M, Stevens RL, Ramirez JM

Author

Erin L. Doren MD Associate Professor in the Plastic Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Animals, Newborn
Computer Simulation
Data Interpretation, Statistical
Electric Stimulation
Electrophysiology
Excitatory Amino Acid Antagonists
Female
Gap Junctions
Male
Mice
Models, Neurological
Neocortex
Nerve Net
Patch-Clamp Techniques
Pyramidal Cells
Riluzole
Sodium Channels
Synapses
Tetrodotoxin