Transcranial pulsed magnetic field stimulation facilitates reorganization of abnormal neural circuits and corrects behavioral deficits without disrupting normal connectivity

FASEB J. 2012 Apr;26(4):1593-606. doi: 10.1096/fj.11-194878. Epub 2012 Jan 5.

Abstract

Although the organization of neuronal circuitry is shaped by activity patterns, the capacity to modify and/or optimize the structure and function of whole projection pathways using external stimuli is poorly defined. We investigate whether neuronal activity induced by pulsed magnetic fields (PMFs) alters brain structure and function. We delivered low-intensity PMFs to the posterior cranium of awake, unrestrained mice (wild-type and ephrin-A2A5(-/-)) that have disorganized retinocollicular circuitry and associated visuomotor deficits. Control groups of each genotype received sham stimulation. Following daily stimulation for 14 d, we measured biochemical, structural (anterograde tracing), and functional (electrophysiology and behavior) changes in the retinocollicular projection. PMFs induced BDNF, GABA, and nNOS expression in the superior colliculus and retina of wild-type and ephrin-A2A5(-/-) mice. Furthermore, in ephrin-A2A5(-/-) mice, PMFs corrected abnormal neuronal responses and selectively removed inaccurate ectopic axon terminals to improve structural and functional organization of their retinocollicular projection and restore normal visual tracking behavior. In contrast, PMFs did not alter the structure or function of the normal projection in wild-type mice. Sham PMF stimulation had no effect on any mice. Thus, PMF-induced biochemical changes are congruent with its capacity to facilitate beneficial reorganization of abnormal neural circuits without disrupting normal connectivity and function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / physiology*
  • Biomarkers / metabolism
  • Brain Mapping
  • Ephrin-A2 / genetics
  • Ephrin-A2 / metabolism
  • Ephrin-A5 / genetics
  • Ephrin-A5 / metabolism
  • Humans
  • Mice
  • Mice, Knockout
  • Nerve Net / abnormalities*
  • Nerve Net / anatomy & histology
  • Nerve Net / physiology*
  • Neuronal Plasticity / physiology
  • Synapses / physiology
  • Transcranial Magnetic Stimulation / methods*
  • Visual Pathways / abnormalities*
  • Visual Pathways / anatomy & histology
  • Visual Pathways / physiology*

Substances

  • Biomarkers
  • Ephrin-A2
  • Ephrin-A5