PKC-epsilon activation is required for recognition memory in the rat

Activation of PKC epsilon, an abundant and developmentally regulated PKC isoform in the brain, has been implicated in memory throughout life and across species. Yet, direct evidence for a mechanistic role for PKC epsilon in memory is still lacking. Hence, we sought to evaluate this in rats, using short-term treatments with two PKC epsilon-selective peptides, the inhibitory epsilon V1-2 and the activating psi epsilon RACK, and the novel object recognition task (NORT). Our results show that the PKC epsilon-selective activator psi epsilon RACK, did not have a significant effect on recognition memory. In the short time frames used, however, inhibition of PKC epsilon activation with the peptide inhibitor epsilon V1-2 significantly impaired recognition memory. Moreover, when we addressed at the molecular level the immediate proximal signalling events of PKC epsilon activation in acutely dissected rat hippocampi, we found that psi epsilon RACK increased in a time-dependent manner phosphorylation of MARCKS and activation of Src, Raf, and finally ERK1/2, whereas epsilon V1-2 inhibited all basal activity of this pathway. Taken together, these findings present the first direct evidence that PKC epsilon activation is an essential molecular component of recognition memory and point toward the use of systemically administered PKC epsilon-regulating peptides as memory study tools and putative therapeutic agents. (C) 2013 Elsevier B.V. All rights reserved.