Stride Made in Understanding Memory

A study submitted to the journal Nature on 16 August 2012 overturns a longheld model of long-term memory formation with the discovery that the protein kinase M, zeta enzyme (PKM-ζ) is not necessary as part of a cellular correlate of learning and memory potentiation/longevity. It was conducted by Lenora J. Volk, Julia L. Bachman, Richard Johnson, Yilin Yu and Richard L. Huganir of the Department of Neuroscience in Howard Hughes Medical Institute at Johns Hopkins University School of Medicine in Baltimore, Maryland.

The abstract notes, "Inhibiting PKM-ζ activity using a synthetic zeta inhibitory peptide (ZIP) based on the PKC-ζ pseudosubstrate sequence reverses established [long-term potentiation (LTP)] in vitro and in vivo. More notably, infusion of ZIP eliminates memories for a growing list of experience-dependent behaviours, including active place avoidance, conditioned taste aversion, fear conditioning and spatial learning. However, most of the evidence supporting a role for PKM-ζ in LTP and memory relies heavily on pharmacological inhibition of PKM-ζ by ZIP. To further investigate the involvement of PKM-ζ in the maintenance of LTP and memory, we generated transgenic mice lacking PKC-ζ and PKM-ζ. We find that both conventional and conditional PKC-ζ/PKM-ζ knockout mice show normal synaptic transmission and LTP at Schaffer collateral–CA1 synapses, and have no deficits in several hippocampal-dependent learning and memory tasks. Notably, ZIP still reverses LTP in PKC-ζ/PKM-ζ knockout mice, indicating that the effects of ZIP are independent of PKM-ζ."