A burning unresolved question in the field of learning and memory is how memories are maintained. Making use of a phenomenon known as long-term potentiation, an experimental tool to study the cellular mechanisms of memory formation, Fonseca and colleagues have now brought us a step closer to the answer.
Electrical stimulation of neurons can result in an artificial increase, or potentiation, in synaptic strength. This is known as long-term potentiation. Fonseca's team knew that potentiation requires protein synthesis, but exactly how the persistence of memory depends on protein synthesis is still a matter of debate. Recent work in this field suggests that `synaptic tags' mark potentiated synapses so that `plasticity factors' are routed to that particular synapse, where the accumulated plasticity factors help stabilize the increase in synaptic strength. The identity of these plasticity factors is unknown, but they are likely to be proteins. Fonseca and colleagues hypothesized that when the availability of these plasticity factors is limited, `tagged' synapses compete for them to the extent that one synapse`loses' and stabilization fails to occur at that synapse.
To test this, Fonseca's team decided to limit plasticity factor resources by inhibiting protein synthesis during long-term potentiation. They first induced long-term potentiation in two independent pathways in adult rat hippocampal slices. Four hours later, the team confirmed that both pathways showed long-term potentiation and then applied a protein synthesis inhibitor to the slices. During protein synthesis inhibition, they weakly stimulated one pathway, thereby reactivating it. They expected this procedure to result in additional short-term potentiation to the already existing potentiation of this reactivated pathway, which is exactly what they saw. However, in the pathway that did not receive the reactivating stimulation (the test pathway),the potentiation immediately started to vanish! In other words, the pathways were indeed competing: the additional potentiation of the reactivated pathway was at the expense of maintaining potentiation of the test pathway. Fonseca and colleagues suspect that the enhancement of the reactivated pathway `uses up' the plasticity factors, compromising stabilization of the test pathway and resulting in the gradual weakening of the test pathway.
This new phenomenon, coined by the authors as `competitive maintenance', is consistent with their view that intracellular competition for plasticity factors is responsible for the persistence of synaptic potentiation. Competition between synapses may provide a means for selective information storage when multiple inputs converge.
That this phenomenon may provide a physiological counterpart of the interference theory of forgetting is highly speculative but exciting. In this view, long-term potentiation induction of the two pathways represents a learning event, and the reactivation of one pathway an interfering event. This leads to competition between the two pathways, thereby weakening the non-reactivated pathway and resulting in forgetting. These speculations, of course, remain to be tested. What is now clear is that plasticity factors are shared according to need among synapses and, under circumstances of reduced availability, competition defines which synapse will win.
