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Persistent Synchronized Bursting Activity in Cortical Tissues With Low Magnesium Concentration: A Modeling Study

¹Department of Physiology and Zlotowski Center for Neuroscience, Faculty of Health Sciences, Ben-Gurion University, Be'er-Sheva, Israel; ²Department of Mathematics, University of Pittsburgh, Pennsylvania; and ³Department of Mathematics, University of Transilvania Brasov, Brasov, Romania

Submitted 7 September 2005; accepted in final form 10 October 2005

We explore the mechanism of synchronized bursting activity with frequency of 10 Hz that appears in cortical tissues at low extracellular magnesium concentration [Mg²⁺]_o. We hypothesize that this activity is persistent, namely coexists with the quiescent state and depends on slow N-methyl-D-aspartate (NMDA) conductances. To explore this hypothesis, we construct and investigate a conductance-based model of excitatory cortical networks. Population bursting activity can persist for physiological values of the NMDA decay time constant (100 ms). Neurons are synchronized at the time scale of bursts but not of single spikes. A reduced model of a cell coupled to itself can encompass most of this highly synchronized network behavior and is analyzed using the fast-slow method. Synchronized bursts appear for intermediate values of the NMDA conductance g_NMDA if NMDA conductances are not too fast. Regular spiking activity appears for larger g_NMDA. If the single cell is a conditional burster, persistent synchronized bursts become more robust. Weakly synchronized states appear for zero AMPA conductance g_AMPA. Enhancing g_AMPA increases both synchrony and the number of spikes within bursts and decreases the bursting frequency. Too strong g_AMPA, however, prevents the activity because it enhances neuronal intrinsic adaptation. When [Mg²⁺]_o is increased, higher g_NMDA values are needed to maintain bursting activity. Bursting frequency decreases with [Mg²⁺]_o, and the network is silent with physiological [Mg²⁺]_o. Inhibition weakly decreases the bursting frequency if inhibitory cells receive enough NMDA-mediated excitation. This study explains the importance of conditional bursters in layer V in supporting epileptiform activity at low [Mg²⁺]_o.

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