Metaplasticity: the plasticity of synaptic plasticity

Activity-dependent modifications of synaptic efficacy are essential both for the developmental organization of the brain and for the storage of information. It is now well established that the pattern of synaptic activation helps direct whether a synapse is strengthened or weakened. For example, in many regions of the brain, high-frequency stimulation (HFS) of afferents results in a long-term potentiation (LTP) of synaptic efficacy, while low-frequency stimulation (LFS) frequently yields long-term depression (LTD) of synaptic strength. However, the direction and degree of this synaptic plasticity is governed by more than simply the pattern of synaptic activation and the, initial synaptic efficacy; prior synaptic activity can shape subsequent use-dependent synaptic modifications. Thus, the plasticity of synapses varies as a function of their activation history. This modulation of synaptic plasticity has been termed ‘metaplasticity’, and accumulating evidence suggests that this phenomenon is a ubiquitous property of the brain, not only in mammals, but in primitive vertebrates and invertebrates as well.