Calmodulin regulates synaptic plasticity in the anterior cingulate cortex and behavioral responses: a microelectroporation study in adult rodents.
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.
Wei
Feng
F
Department of Anesthesiology, Anatomy and Neurobiology, and Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA. fwei001@umaryland.edu
Xia
Xia-Ming
XM
Tang
Jianrong
J
Ao
Hushan
H
Ko
Shanelle
S
Liauw
Jason
J
Qiu
Chang-Shen
CS
Zhuo
Min
M
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D002147:Calmodulin / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D018274:Electroporation / Q000379:methods*; D015870:Gene Expression / Q000502:physiology; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins; D006179:Gyrus Cinguli / Q000502:physiology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000235:genetics / Q000502:physiology; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008845:Microinjections; D009043:Motor Activity / Q000235:genetics; D009154:Mutation; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism*
D002147:Calmodulin; D018076:DNA, Complementary; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins