Abstracts

Rationale: DBS has been used or investigated for various neuropsychiatric disorders. However, its mechanism of action remains poorly understood. The aim of this trial is to increase our knowledge on this issue. Methods: The effect of hippocampal high-frequency (130 Hz) DBS on hippocampal excitability was evaluated in freely moving healthy rats by means of Schaffer collateral-CA1 EPs. During the 'acute' experiments, DBS was administered in 10-min duty cycles with 1-6 minutes of DBS per cycle. During DBS-free intervals EPs were evoked every 20 seconds starting 2 to 100 msec after the last DBS pulse. EPs were averaged based on their timing relative to the last DBS pulse (0,1-220 s) as well as per duty cycle (16 in total). This allowed us to evaluate both short temporary effects and more sustained direct effects. The 'chronic' experiment consisted of a 2-day baseline period, 2 days of continous DBS and a washout period. Input-output curves were performed 3x per day. Results: Effects of DBS during the 'acute' experiments were only very limited. Compared to sham stimulation, DBS was associated with a discrete temporary reduction of the 10% field excitatory post-synaptic potential (fEPSP) (< 1 minute). Over successive duty cycles, DBS resulted in a more sustained but still mild fEPSP and population spike (PS) reduction. In contrast, a strong fEPSP reduction was seen during chronic DBS, especially for the low-intensity EPs. The PS reduction seemed even more pronounced, but this was only secondarily to the reduced fEPSP as the fEPSP-PS relationship ('intrinsic excitability') remained largely unchanged. An entire week was needed for fEPSP and PS values to return to baseline figures. When DBS was administered through a separate stimulation electrode (different from the EP stimulation electrode), no effects were seen. Conclusions: Short-term high-frequency DBS has only limited effects on hippocampal excitability as evaluated by intrahippocampal EPs. Longer stimulation, however, is associated with a marked and long-lasting but focal reduction of the fEPSP with unaltered intrinsic excitability. Funding: Funding: Mathieu Sprengers is supported by an FWO-aspirant grant (Research Foundation of Flanders).