Signaling components in rat hippocampal slices: Effects of protease inhibition

Abstract

We performed extracellular recording in the CA1 field of acute hippocampal slices of Wistar rats and measured presynaptic volley, EPSP slope, and population spike amplitude after the stimulation of the Schaffer collaterals of different intensities. A comparison of the maximum responses in slices that were preincubated with caspase-3 (Z-DEVD-FMK) or cathepsin B (Z-FA-FMK) inhibitors did not show any significant differences in the indices studied. It is difficult to reveal the effects of caspase inhibitors because its substrates in different compartments can participate in signal transmission. We approximated the relationships between the presynaptic volley, fEPSP slope, and population spike amplitude and the stimulus intensity using several functions. The parameters of these functions were calculated for each slice individually. Mathematical modeling suggests that all function parameters are typical of different mechanisms of neuronal responses. The correlations between the theoretical functions and experimental data were highly significant for the majority of slices. This method confirmed the possibility of synaptic potentiation after caspase-3 inhibition under both excitotoxic and nonpathological in vitro conditions. In the presence of cathepsin B inhibitors, the approximating functions had parameters that reflected the increased excitability of CA1 pyramidal neurons. The majority of the other parameters did not differ in the control, Z-DEVD-FMK and Z-FA-FMK groups, or were significantly the same.