Persistent synchronized bursting activity in cortical tissues with low magnesium concentration: a modeling study.
We explore the mechanism of synchronized bursting activity with frequency of approximately 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 (approximately 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.
Golomb
David
D
Department of Physiology, Faculty of Health Sciences, Ben-Gurion University, Be'er-Sheva, Israel. golomb@bgu.ac.il
Shedmi
Anat
A
Curtu
Rodica
R
Ermentrout
G Bard
GB
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002540:Cerebral Cortex / Q000502:physiology*; D003198:Computer Simulation; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D008274:Magnesium / Q000378:metabolism*; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology*; D010507:Periodicity; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D013997:Time Factors
D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D008274:Magnesium