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

Exp Brain Res. 2008 Jun;188(2):249-61. doi: 10.1007/s00221-008-1356-2. Epub 2008 Apr 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism*
  • Brain / radiation effects*
  • Brain Mapping
  • Cell Count
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / radiation effects
  • Early Growth Response Protein 1 / metabolism*
  • Electromagnetic Fields*
  • Evoked Potentials / genetics
  • Evoked Potentials / radiation effects
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / radiation effects
  • Genes, Immediate-Early / genetics
  • Genes, Immediate-Early / radiation effects
  • Immunohistochemistry
  • Limbic System / metabolism
  • Limbic System / radiation effects
  • Male
  • Nerve Net / metabolism
  • Nerve Net / radiation effects
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Rats
  • Transcranial Magnetic Stimulation / methods*


  • Early Growth Response Protein 1
  • Egr1 protein, rat
  • Proto-Oncogene Proteins c-fos