Pining for things past

Long-term memories are thought to be maintained by persistent changes in the strength of synaptic connections among neurons, but how such changes can persist for days to years has been one of the fundamental enigmas of neuroscience. Recently, however, one mechanism that is dependent on the persistent increased activity of an enzyme has been shown to be necessary for the persistence of long-term memory. The transient inhibition of the brain-specific, constitutively active protein kinase C isoform PKMζ erases memories that are even months old. This finding raises a number of issues; chief among them is the question, how can PKMζ maintain memories for months when its half-life is probably much shorter? New data suggest how the high abundance of PKMζ can be maintained over long periods of time. The synthesis of PKMζ is inhibited by Pin1 (protein interacting with NIMA 1), a peptidyl-prolyl isomerase that represses dendritic translation. Signals mediated by the excitatory neurotransmitter glutamate, which induces long-term potentiation (LTP) and memory formation, inhibit Pin1, enabling PKMζ synthesis. PKMζ, once translated, in turn inhibits Pin1, permitting persistent PKMζ synthesis. In this way, PKMζ may be up-regulated to the appropriate amounts for maintaining LTP and perpetuating our mental representations of the past.