Griffith L C, Verselis L M, Aitken K M, Kyriacou C P, Danho W, Greenspan R J
Department of Neurosciences, Roche Institute of Molecular Biology, Nutley, New Jersey 07110.
Neuron. 1993 Mar;10(3):501-9. doi: 10.1016/0896-6273(93)90337-q.
One of the major mediators of calcium action in neurons is the multifunctional calcium/calmodulin-dependent protein kinase (CaM kinase), an enzyme with the capability of directly regulating its own activity by autophosphorylation. To assess the involvement of CaM kinase in experience-dependent behavior in an intact animal, we have designed a specific peptide inhibitor of CaM kinase and made transgenic Drosophila that express it under control of an inducible promoter. These flies fail to learn normally in two behavioral plasticity paradigms: acoustic priming, a nonassociative measure of sensitization, and courtship conditioning, a measure of associative learning. The magnitude of the learning defect in the associative paradigm appears to be proportional to the level of expression of the peptide gene in the two transgenic lines and can be increased by heat shock induction of gene expression. These results suggest that CaM kinase activity is required for plastic behaviors in an intact animal.
神经元中钙作用的主要介质之一是多功能钙/钙调蛋白依赖性蛋白激酶（CaM激酶），这是一种能够通过自身磷酸化直接调节其自身活性的酶。为了评估CaM激酶在完整动物的经验依赖性行为中的作用，我们设计了一种CaM激酶的特异性肽抑制剂，并制作了在可诱导启动子控制下表达该抑制剂的转基因果蝇。这些果蝇在两种行为可塑性范式中无法正常学习：声学启动，一种非联想性的敏感化测量方法，以及求偶条件反射，一种联想学习的测量方法。在联想范式中学习缺陷的程度似乎与两个转基因系中肽基因的表达水平成正比，并且可以通过热休克诱导基因表达而增加。这些结果表明，CaM激酶活性是完整动物可塑性行为所必需的。
