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NEUROSCIENCE
The protein PKM-æ has been proposed to regulate the maintenance of memory in rodents, but this theory has been questioned. The finding that another isoform of the protein acts as a backup if PKM-æ is lacking will influence this debate.
An understanding of memory has long been a goal of neuroscience. One question that has attracted particular attention is whether there is a specific molecule that maintains memories. After almost two decades of careful work, neuroscientist Todd Sacktor and colleagues thought they had the answer. In 2006, the authors reported1 that an atypical isoform of the enzyme protein kinase C, called PKM-ζ, was involved in maintaining memories in mice, and that an inhibitor of PKM-ζ could erase memories. The results were subsequently questioned2,3, and controversy ensued. Writing in eLife, the same group that performed the 2006 study opens a new chapter in this debate4, arguing that PKM-ζ should be restored to its pre-eminent status as the memory molecule.
More than half a century ago, the psychologist Donald Hebb proposed that the synaptic connections between two neurons are strengthened when the neurons fire together5. He suggested that this form of synaptic strengthening provided the basis for the formation of long-term memories, enabling many neurons to be linked together in cell assemblies that serve as the physical substrates of memory, called engrams. It was later discovered6 that high-frequency neural stimulation led to persistent increases in synaptic strength, known as long-term potentiation (LTP). Most neuroscientists embraced the idea that understanding LTP was the key to understanding memory7. The race was on to identify the molecular machinery involved in LTP.
One molecule in particular emerged from the fray. Although dozens of molecules were involved in initial synaptic strengthening following high-frequency...