Activity-dependent changes of tissue resistivity in the CA1 region in vivo are layer-specific: modulation of evoked potentials

Abstract

We have investigated the spatial map of tissue resistivity across CA1 layers in vivo, its modifications during repetitive orthodromic activity, and the influence of this factor on the shaping of population spikes. Measurement of tissue resistance was made by a high-spatial-resolution three-electrode method. A computer network of equivalent resistors aided theoretical analysis. Tissue resistivity was homogeneous within the basal and apical dendritic trees (260±4.5 and 287±2.6 Ωcm, respectively). In the stratum pyramidale we found a sharply delimited high-resistivity (643±35 Ωcm) band ∼20 μm wide. Resistivity in slices was ∼30% higher than in vivo. Computer analysis indicated that the high-resistance somatic layer has a strong influence on the somatic and proximal dendritic contribution to the shaping of population spikes, and reduces volume propagation of currents between dendritic trees. Repetitive orthodromic activation at the theta frequency (4–5 Hz, 20–30 s) caused a stereotyped cycle of field potentials and layer-specific changes of resistivity. Initially (∼10 s), long-lasting field excitatory postsynaptic potentials and multiple somatodendritic population spikes developed, and resistivity gradually increased in all layers at a similar rate (period average: 11%). Subsequently, the long-lasting field excitatory synaptic potential subsided and dendritic spike generators were strongly reduced, but multiple somatic spikes remained. Concurrently, the resistivity reached a plateau in all dendritic layers but continued to increase in the somatic layer for about 10–15 s (20% average and up to 50% maximum). Recovery required ∼60 s. The orthodromic somatic population spike increased variably during stimulation (up to 60%). Using local resistivity changes for correction, supernormal increments of the population spikes were offset, but not totally, uncovering several sub- and supernormal phases that were partially related to changes in dendritic population spike. These resistivity-independent modulations of the somatic population spike are caused by variable volume spread from dendritic spike currents and changed somatic contribution of firing units. This report demonstrates that the strong heterogeneity in the stratum pyramidale is an important factor shaping and modulating the population spike. The different regional rates of resistivity variation force the independent correction of local evoked potentials. We show that not doing so may cause bulk errors in the interpretation of, for instance, field potential ratios widely used to measure the population excitability. The present results underscore the importance of checking variations in recording conditions, which are inherent in most experimental protocols.