Longitudinal Depolarization Gradients Along the Somatodendritic Axis of CA1 Pyramidal Cells: A Novel Feature of Spreading Depression

Abstract

We studied the subcellular correlates of spreading depression (SD) in the CA1 rat hippocampus by combining intrasomatic and intradendritic recordings of pyramidal cells with extracellular DC and evoked field and unitary activity. The results demonstrate that during SD only specific parts of the dendritic membranes are deeply depolarized and electrically shunted. Somatic impalements yielded near-zero membrane potential ( Vm) and maximum decrease of input resistance ( Rin) whether the accompanying extracellular negative potential ( Vo) moved along the basal, the apical or both dendritic arbors. However, apical intradendritic recordings showed a different course of local Vm that is hardly detected from the soma. A decreasing depolarization gradient was observed from the edge of SD-affected fully depolarized subcellular regions toward distal dendrites. Within apical dendrites, the depolarizing front moved toward and stopped at proximal dendrites during the time course of SD so that distal dendrites had repolarized in part or in full by the end of the wave. The drop of local Rin was initially maximal at any somatodendritic loci and also recovered partially before the end of SD. This recovery was stronger and faster in far dendrites and is best explained by a wave-like somatopetal closure of membrane conductances. Cell subregions far from SD-affected membranes remain electrically excitable and show evoked unitary and field activity. We propose that neuronal depolarization during SD is caused by current flow through extended but discrete patches of shunted membranes driven by uneven longitudinal depolarization.