Contribution of persistent Na+ current and M-type K+ current to somatic bursting in CA1 pyramidal cells: combined experimental and modeling study.
The intrinsic firing modes of adult CA1 pyramidal cells vary along a continuum of "burstiness" from regular firing to rhythmic bursting, depending on the ionic composition of the extracellular milieu. Burstiness is low in neurons exposed to a normal extracellular Ca(2+) concentration ([Ca(2+)](o)), but is markedly enhanced by lowering [Ca(2+)](o), although not by blocking Ca(2+) and Ca(2+)-activated K(+) currents. We show, using intracellular recordings, that burstiness in low [Ca(2+)](o) persists even after truncating the apical dendrites, suggesting that bursts are generated by an interplay of membrane currents at or near the soma. To study the mechanisms of bursting, we have constructed a conductance-based, one-compartment model of CA1 pyramidal neurons. In this neuron model, reduced [Ca(2+)](o) is simulated by negatively shifting the activation curve of the persistent Na(+) current (I(NaP)) as indicated by recent experimental results. The neuron model accounts, with different parameter sets, for the diversity of firing patterns observed experimentally in both zero and normal [Ca(2+)](o). Increasing I(NaP) in the neuron model induces bursting and increases the number of spikes within a burst but is neither necessary nor sufficient for bursting. We show, using fast-slow analysis and bifurcation theory, that the M-type K(+) current (I(M)) allows bursting by shifting neuronal behavior between a silent and a tonically active state provided the kinetics of the spike generating currents are sufficiently, although not extremely, fast. We suggest that bursting in CA1 pyramidal cells can be explained by a single compartment "square bursting" mechanism with one slow variable, the activation of I(M).
Golomb
David
D
Department of Physiology and Zlotowski Center for Neuroscience, Faculty of Health Sciences, Ben-Gurion University, Be'er-Sheva, Israel. golomb@bgu.ac.il
Yue
Cuiyong
C
Yaari
Yoel
Y
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