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The Journal of Neuroscience, September 10, 2003, 23(23):8402-8409
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Calmodulin Regulates Synaptic Plasticity in the Anterior Cingulate Cortex and Behavioral Responses: A Microelectroporation Study in Adult Rodents
Feng Wei,1,2
Xia-Ming Xia,1
Jianrong Tang,1
Hushan Ao,1
Shanelle Ko,1,3
Jason Liauw,1
Chang-Shen Qiu,1 and
Min Zhuo1,3
1Departments of Anesthesiology, Anatomy and Neurobiology, and Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, 2Department of Oral and Craniofacial Biological Sciences, University of Maryland Dental School, Baltimore, Maryland 21201, and 3Department of Physiology, University of Toronto, Toronto, Canada, M5S 1A8
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.
Key words: calmodulin; electroporation; gene transfer; anterior cingulate cortex; synaptic plasticity; mice
Received Feb 4, 2003;
revised July 16, 2003;
accepted July 16, 2003.
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