Memory and the single molecule

Abstract

Sustained activity of the brain-specific enzyme PKM-ζ is thought to underlie the maintenance of long-term memories. Studies in PKM-ζ-deficient mice, however, cast the importance of this protein into question. See Letters p.416 & p.420 Long-term potentiation (LTP), a persistent enhancement of signalling between nerve cells, has long been considered the likely cellular correlate of memory, but only now are the specific molecular mechanisms underlying the maintenance of LTP beginning to emerge. Some time ago, it was proposed that sustained activity of protein kinase M-ζ (PKM-ζ) may be a key factor in sustaining LTP, based mainly on experiments using pharmacological inhibitors. Two groups have now engineered mice lacking PKM-ζ to test more directly for its role in LTP and memory. Studies from the labs of Richard Huganir and Robert Messing find that loss of PKM-ζ has no effect on LTP or memory formation. And despite the absence of this kinase, pharmacological inhibitors of PKM-ζ still disrupt memory in these mutant mice. These data cast doubt on the role of PKM-ζ in LTP maintenance and re-open the exploration for key molecules regulating long-term plasticity.