Frequency-Dependent Inhibition Induced by Stimulations in Rat Hippocampus

Deep brain stimulation (DBS) has a good prospect in treating brain diseases such as epilepsy. However, its therapeutic mechanism is undetermined yet. To investigate the inhibitory effects of DBS acting on the downstream neurons in target region, 1-min pulse trains of orthodromic stimulations with various frequencies (10 - 100 Hz) were applied to the Schaffer collaterals of hippocampal CA1 region in anaesthetized rats. Unit spikes of downstream interneurons and pyramidal cells were detected and analyzed. Interneurons activated by the stimulation through mono-synaptic connections were recognized based on short latencies. Their firing was used as an index of stimulation-induced inhibition. Results showed that during stimulations with pulse frequency of 20 Hz, the mean firing rate of mono-synaptically-activated interneurons was significantly higher than the value during 10 Hz stimulations. Afterward, even if the pulse frequency increased to 100 Hz, the mean firing rate of the interneurons did not change significantly. However, only during stimulations with lower frequencies (10, 20 Hz), the firing of pyramidal cells was suppressed by the stimulation-activated interneurons. The inhibitory effects of interneurons were weakened during stimulations with higher frequencies (50 and 100 Hz). De-synchronous firing of interneurons induced by high-frequency stimulation might cause the loss of effective inhibition on the principal neurons. These findings provide new information for advancing the application of DBS.