Dose and time-dependence of acute intermittent theta-burst stimulation on hippocampus-dependent memory in parkinsonian rats

The treatment options for cognitive impairments in Parkinson's disease (PD) are limited. Repetitive transcranial magnetic stimulation has been applied in various neurological diseases. However, the effect of intermittent theta-burst stimulation (iTBS) as a more developed repetitive transcranial magnetic stimulation paradigm on cognitive dysfunction in PD remains largely unclear. Our aim was to explore the effect of acute iTBS on hippocampus-dependent memory in PD and the mechanism underlying it. Different blocks of iTBS protocols were applied to unilateral 6-hydroxidopamine-induced parkinsonian rats followed by the behavioral, electrophysiological and immunohistochemical analyses. The object-place recognition and hole-board test were used to assess hippocampus-dependent memory. Sham-iTBS and 1 block-iTBS (300 stimuli) didn't alter hippocampus-dependent memory, hippocampal theta rhythm and the density of c-Fos- and parvalbumin-positive neurons in the hippocampus and medial septum. 3 block-iTBS (900 stimuli) alleviated 6-hydroxidopamine-induced memory impairments, and increased the density of hippocampal c-Fos-positive neurons at 80 min post-stimulation but not 30 min compared to sham-iTBS. Interestingly, 3 block-iTBS first decreased and then increased normalized theta power during a period of 2 h following stimulation. Moreover, 3 block-iTBS decreased the density of parvalbumin-positive neurons in the medial septum at 30 min post-stimulation compared to sham-iTBS. The results indicate that multiple blocks of iTBS elicit dose and time-dependent effects on hippocampus-dependent memory in PD, which may be attributed to changes in c-Fos expression and the power of theta rhythm in the hippocampus.