Abstract
Synaptic plasticity is a critical underlying mechanism of learning and memory. There is extensive evidence that neural activity at one point in time can affect the properties of subsequent synaptic plasticity (for example, whether a synapse becomes potentiated or depressed, and for how long). That is, synaptic plasticity itself can be dynamically regulated by the prior history of activity. Such “metaplasticity” can be expressed homosynaptically, heterosynaptically, or even heterodendritically. We have studied a form of heterodendritic metaplasticity in the hippocampus that regulates future plasticity via an intercellular signaling cascade, including astrocytes, that culminates in long-term potentiation (LTP) inhibition and long-term depression (LTD) facilitation. Conversely, the synaptic tag and capture hypothesis is a form of intracellular metaplasticity in which the duration of synaptic plasticity is centrally regulated by protein synthesis such that prior neural activity facilitates the longevity of LTP and LTD, either heterosynaptically or heterodendritically. Although on the surface, both mechanisms appear similar in their ability to confer cell-wide regulation of synaptic plasticity, these mechanisms appear somewhat at odds with one another. In this review, we discuss the underlying mechanisms of these two distinct regulatory mechanisms and their potential roles in learning and memory.