High- and low-frequency repetitive transcranial magnetic stimulation differentially activates c-Fos and zif268 protein expression in the rat brain

Repetitive transcranial magnetic stimulation (rTMS) has been shown to alter cortical excitability depending on the stimulus-frequency used, with high frequency (5 Hz and higher) increasing it but low frequency (usually 1 Hz or lower) reducing it. To determine the efficiency of different rTMS protocols in inducing cortical network activity, we tested the acute effect of one low-frequency rTMS protocol (1 Hz) and two different high-frequency protocols (10 Hz and intermittent theta-burst stimulation, iTBS) on the expression of the two immediate early gene (IEG) proteins c-Fos and zif268 in the rat brain. The cortical expression of both IEGs was specifically changed in an rTMS-dependent manner. One and 10 Hz rTMS enhanced c-Fos protein expression in all cortical areas tested, while iTBS was effective only in limbic cortices. Zif268 expression was increased in almost all cortical areas after iTBS, while 10 Hz rTMS was effective only in the primary motor and sensory cortices. One Hertz rTMS had no effect on cortical zif268 expression. Furthermore, sham-rTMS had no effect on zif268 expression but increased c-Fos in limbic cortices. This is the first study demonstrating that cortical zif268 and c-Fos expression can be specifically modulated by acute rTMS depending on the pattern of stimulation applied.