Calmodulin regulates synaptic plasticity in the anterior cingulate cortex and behavioral responses: a microelectroporation study in adult rodents

J Neurosci. 2003 Sep 10;23(23):8402-9. doi: 10.1523/JNEUROSCI.23-23-08402.2003.


We developed a microelectroporation method for the transfer of genes into neurons in the cerebral cortex of adult rodents, both rats and mice. We selectively expressed either green-fluorescent protein (GFP) or a Ca2+-binding deficient calmodulin (CaM) mutant in the anterior cingulate cortex (ACC). In mice that expressed GFP, positive neuronal cell bodies were found specifically at the injection site in the ACC. Mice that expressed CaM12, a mutant CaM with two impaired Ca2+ binding sites in the N-terminal lobe, exhibited significant changes in vocalization, locomotion, and sensory functions. Long-term potentiation and long-term depression, two major forms of central plasticity, were completely abolished by expression of CaM12. Mice that expressed CaM34, a mutant CaM with two impaired Ca2+ binding sites in the C-terminal lobe, did not show any significant behavioral or electrophysiological alterations. These findings provide strong evidence that CaM is critical for bidirectional synaptic plasticity. This new method will be useful for investigating gene function in specific brain regions of freely moving animals. Furthermore, this approach also may facilitate gene therapy in adult human brains.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal / physiology*
  • Calmodulin / genetics
  • Calmodulin / metabolism*
  • DNA, Complementary / genetics
  • DNA, Complementary / pharmacology
  • Electric Stimulation / methods
  • Electroporation / methods*
  • Gene Expression / physiology
  • Gene Transfer Techniques
  • Green Fluorescent Proteins
  • Gyrus Cinguli / physiology*
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • In Vitro Techniques
  • Long-Term Potentiation / genetics
  • Long-Term Potentiation / physiology
  • Long-Term Synaptic Depression / genetics
  • Long-Term Synaptic Depression / physiology
  • Luminescent Proteins / biosynthesis
  • Luminescent Proteins / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microinjections
  • Motor Activity / genetics
  • Mutation
  • Neuronal Plasticity / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Synapses / metabolism*


  • Calmodulin
  • DNA, Complementary
  • Luminescent Proteins
  • Green Fluorescent Proteins