Repeated anodal transcranial direct current stimulation induces neural plasticity-associated gene expression in the rat cortex and hippocampus

Restor Neurol Neurosci. 2017;35(2):137-146. doi: 10.3233/RNN-160689.


Background: Anodal transcranial direct current stimulation (A-tDCS) induces a long-lasting increase in cortical excitability that can increase gene transcription in the brain.

Objective: The purpose of this study was to evaluate the expression of genes related to activity-dependent neuronal plasticity in the sensorimotor cortex and hippocampus of young Sprague-Dawley rats following A-tDCS.

Methods: We applied A-tDCS over the right sensorimotor cortex epicranially with a circular electrode (3 mm diameter) at 250 μA for 20 min per day for 7 consecutive days. Levels of mRNA for brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), synapsin I, Ca2+/calmodulin-dependent protein kinase II (CaMKII), activity-regulated cytoskeleton-associated protein (Arc), and c-Fos were analyzed using SYBR Green quantitative real-time polymerase chain reaction (PCR).

Results: We found that 7 days of unilateral A-tDCS resulted in significant increases in transcription of all plasticity-related genes tested in the ipsilateral cortex. Daily A-tDCS also resulted in a significant increase in c-Fos mRNA in the ipsilateral hippocampus.

Conclusion: These results indicate that altered expression of plasticity-associated genes in the cortex and hippocampus is a molecular substrate of A-tDCS-induced neural plasticity.

Keywords: Anodal transcranial direct current stimulation; immediate-early genes; somatosensory cortex; synaptic plasticity-related genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • CREB-Binding Protein / genetics
  • CREB-Binding Protein / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Cerebral Cortex / metabolism*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Electrodes
  • Gene Expression / physiology*
  • Hippocampus / metabolism*
  • Male
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neuronal Plasticity / physiology*
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Synapsins / genetics
  • Synapsins / metabolism
  • Transcranial Direct Current Stimulation*


  • Brain-Derived Neurotrophic Factor
  • Cytoskeletal Proteins
  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Synapsins
  • activity regulated cytoskeletal-associated protein
  • CREB-Binding Protein
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2