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

Abstract

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.

Theta-Burst Transcranial Magnetic Stimulation Alters Cortical Inhibition

“…6), indicating that iTBS had initiated a fast activity-dependent degradation process for PV, most likely via the proteasome system. In a previous study, we could already show that iTBS also increased the cortical expression of zif268 (Aydin-Abidin et al, 2008), an immediate early gene product which is increased along with long-term synaptic potentiation, and is supposed to increase the proteasome activity (Baumgärtel et al, 2009).…”

“…Stimulus strength was adjusted to be just subthreshold for evoking visible activity in neck and limb muscles. This range of stimulation strength had previously been found to be perithreshold for modulating spiking activity in cat visual cortex (Moliadze et al, 2003) and induced specific changes in immediate early gene expression in a previous study in rats (Aydin-Abidin et al, 2008). The distance between coil and rat cortex was increased to 8 cm in case of sham stimulation.…”

Effects of Transcranial Direct Current Stimulation on Expression of Immediate Early Genes (IEG's)

“…Experiments in TMS (transcranial magnetic stimulation) show differential expression of zif268 and cFos due to stimulation 9 . Both genes responded to stimulation, but to different stimulation parameters.…”

“…In case of our first experiment, in which awake animals were placed in a novel object arena during stimulation; this could have contributed to why we saw zif268 induction and not cFos. Researchers investigated expression levels of cFos and zif268 with TMS treatment and how it was modulated with different stimulation parameters 9 . They showed that current involving intermittent thetaburst throughout stimulation induced the expression of zif268, but not cFos when compared against sham values 9 .…”

Effects of Repetitive Transcranial Magnetic Stimulation on Dystonia: An Overview

“…It has been suggested that LTP-and long-term depression (LTD)-like mechanisms as well as GABAergic activity are involved in the effects of rTMS protocols (Ziemann, 2004;Thickbroom, 2007). Animal studies suggest that modulation of neurotransmitters and gene induction may contribute to the long-lasting modulatory effects of rTMS (Hallett, 2007;Kobayashi and Pascual-Leone, 2003;Arias-Carrion, 2008;Aydin-Abidin et al, 2008;Murillo-Rodriguez et al, 2009).…”