期刊
EUROPEAN JOURNAL OF NEUROSCIENCE
卷 27, 期 2, 页码 444-456出版社
WILEY
DOI: 10.1111/j.1460-9568.2008.06022.x
关键词
computer model; current source density; DC potential; rat; slow potentials; tissue resistivity
Spreading depression (SD), a wave of neuron activity related to migraine and the ischaemic penumbra, features a moving shell of extracellular negative potential shift (V-o) whose generators are poorly understood. We investigated its subcellular correlates in the hippocampal CA1 in vivo by localizing the neuron domains that generate transmembrane current (I-m) using field analysis, and the local changes of tissue resistivity, a major determinant of extracellular current flow. A large increase of tissue resistivity occurred in times and dendritic strata displaying large V-o, albeit with different rates. Typically, SD is composed of basal and apical dendritic components. The apical SD lasts much longer, while it becomes gradually restricted to a narrow dendritic region. Strikingly, pyramidal cells displayed a strong surge of inward current only when SD affected a small dendritic region. However, when the V-o signal covered most of the main neuron axis, only smaller surges of inward current developed at the outer dendritic rims of a wide null current zone. Computational reconstruction showed that this effect was due to strong spatial cancellation of the inward and outward currents in SD-activated isopotential and shunted regions of individual neurons. Consequently, despite former accounts of large conductance increase, the net I-m is small and the large Delta V-o amplitude mostly due to increased tissue resistivity. The particular subcellular evolution indicates an initial explosive opening of conductance along most of the pyramidal neuron followed by a wave-like centripetal closure towards the apical dendrites. The applicability of these mechanisms to SD in other brain regions is discussed.
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