The induction of homo- vs heterosynaptic LTD in area CA1 of hippocampal slices from adult rats

The induction of long-term depression (LTD) was investigated in area CA1 of hippocampal slices from adult rats. To produce LTD, prolonged low-frequency stimulation (LFS, 900 stimuli at 1 Hz) was delivered to one of two independent Schaffer-collateral/commissural projections, while the second input served as a control to monitor heterosynaptic effects. The depression was calculated as percent decrease in the slope of the dendritic field EPSP relative to baseline values, and LTD was considered established if the response decrement was at least 15% in magnitude and stable for 30-60 min. By delivering LFS in conditions of different relative baseline response magnitudes, it was revealed that the intensity of afferent low-frequency activity has a significant impact on the induction frequency, magnitude and input-specificity of the depression: the rate of LTD occurrence and the effect of LFS on the absolute response decrement increased successively as the stimulation strength was raised, but the impact of LFS on the relative LTD magnitude decreased at higher stimulation intensities; the depression was specific to the stimulated input (homosynaptic LTD) when baseline responses were spike-free, but spread to the pathway which was silent during LFS (heterosynaptic LTD) in experiments conducted above spiking threshold. The results indicate that in the adult rat (i) the induction of input-specific LTD is dependent on the level of synaptic activation during LFS, and (ii) LTD can easily be obtained in strongly stimulated pathways but may be the result of a generalized decrease in the postsynaptic response.