Rapid Erasure of Long-Term Memory Associations in the Cortex by an Inhibitor of PKM{zeta}
Reut Shema, Todd Charlton Sacktor, Yadin Dudai

Little is known about the neuronal mechanisms that subserve long-term memory persistence in the brain. The components of the remodeled synaptic machinery, and how they sustain the new synaptic or cellwide configuration over time, are yet to be elucidated. In the rat cortex, long-term associative memories vanished rapidly after local application of an inhibitor of the protein kinase C isoform, protein kinase M zeta (PKM{zeta}). The effect was observed for at least several weeks after encoding and may be irreversible. In the neocortex, which is assumed to be the repository of multiple types of long-term memory, persistence of memory is thus dependent on ongoing activity of a protein kinase long after that memory is considered to have consolidated into a long-term stable form.

The authors used conditioned taste aversion (you may be familiar with this learning paradigm if you've ever made yourself sick off tequila). Injection of a peptide inhibitor of this enzyme (PKM zeta) completely removed the aversive association. This isn't a paper about how to erase memories for any clinical application because, for instance, injecting the drug erases multiple olfactory associations (i.e. we don't have a clue how to achieve specificity). It is a paper about how memory works, and it is pretty remarkable that a simple mechanism like persistent kinase activation may be central to this neural function.

Labels: Memory, PKM Zeta

The new Showtime version of This American Life has a segment featuring Todd Sacktor and Andre Fenton. They published a remarkable paper (discussed on gnxp) last year showing that specific inhibition of PKM Zeta (a consitutively active version of protein kinase C) can erase memories. This is all in rats of course. So if you have Showtime, it'll air tomorrow night, Thursday the 26th.

Labels: PKM Zeta