Laboratory of Physiology
University of Oxford, Parks Road, Oxford, Oxfordshire OX1 3PT
UK
Long-term memory storage depends on transcription in the nucleus, an organelle shared by all synapses of a neuron. This raises a question: Are long-term changes cell-wide, or can induced gene products be spatially compartmentalized so that they selectively alter the function of some synapses and not others? In Aplysia, a neuron-specific isoform of cytoplasmic polyadenylation element–binding protein (CPEB) regulates local synaptic protein synthesis. Local protein synthesis serves two functions: (1) it marks the activated synapse and thus confers synapse specificity, and (2) it stabilizes the synaptic growth associated with long-term memory. CPEB may serve as a stabilizer because it has prion-like properties. Prion proteins have the unusual ability to fold into functionally distinct conformations, one of which is self-perpetuating. The dominant, prion-like form of CPEB has the greatest capacity to stimulate translation of CPEB-regulated mRNA. Conversion of CPEB to a prion-like state in stimulated synapses may help to maintain long-term synaptic changes associated with memory storage.
Eric R. Kandel is University Professor and Director of the Kavli Institute for Brain Science at Columbia University’s College of Physicians and Surgeons and an Investigator of the Howard Hughes Medical Institute. He received the 2000 Nobel Prize in Physiology or Medicine.