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The Journal of Neuroscience, August 15, 2000, 20(16):5906-5914

A Role for the  Isoform of Protein Kinase C in Fear Conditioning

Edwin J. Weeber¹, Coleen M. Atkins¹, Joel C. Selcher¹, Andrew W. Varga¹, Banafsheh Mirnikjoo¹, Richard Paylor^{1, 2}, Michael Leitges³, and J. David Sweatt¹

¹  Division of Neuroscience and ²  Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, and ³  Institut for Immunbiologie, Max Planck Institute, 79108 Freiburg, Germany

The protein kinase C family of enzymes has been implicated in synaptic plasticity and memory in a wide range of animal species, but to date little information has been available concerning specific roles for individual isoforms of this category of kinases. To investigate the role of the  isoform of PKC in mammalian learning, we characterized mice deficient in the PKC gene using anatomical, biochemical, physiological, and behavioral approaches. In our studies we observed that PKC was predominantly expressed in the neocortex, in area CA1 of the hippocampus, and in the basolateral nucleus of the amygdala. Mice deficient in PKC showed normal brain anatomy and normal hippocampal synaptic transmission, paired pulse facilitation, and long-term potentiation and normal sensory and motor responses. The PKC knock-out animals exhibited a loss of learning, however; they suffered deficits in both cued and contextual fear conditioning. The PKC expression pattern and behavioral phenotype in the PKC knock-out animals indicate a critical role for the  isoform of PKC in learning-related signal transduction mechanisms, potentially in the basolateral nucleus of the amygdala.

Key words: PKC; Pavlovian fear conditioning; hippocampus; amygdala; knock-out; mice

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20165906-09$05.00/0

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