Abstract
Long-term potentiation in hippocampal neurons has stages that correspond to the stages of learning and memory. Early-phase (10–30 min) potentiation is accompanied by rapid increases in clusters or puncta of presynaptic and postsynaptic proteins, which depend on actin polymerization but not on protein synthesis. We have now examined changes in pre- and postsynaptic puncta and structures during glutamate-induced late-phase (3 hr) potentiation in cultured hippocampal neurons. We find that (1) the potentiation is accompanied by long-lasting maintenance of the increases in puncta, which depends on protein synthesis, (2) most of the puncta and synaptic structures are very dynamic, continually assembling and disassembling at sites that are more stable than the puncta or structures themselves, (3) the increase in presynaptic puncta appears to be due to both rapid and more gradual increases in the number of sites where the puncta may form, and also to the stabilization of existing puncta, (4) under control conditions, puncta of postsynaptic proteins behave similarly to puncta of presynaptic proteins and share sites with them, and (5) the increase in presynaptic puncta is accompanied by a similar increase in presumably presynaptic structures, which may form at distinct as well as shared sites. The new sites could contribute to the transition between the early and late phase mechanisms of plasticity by serving as seeds for the formation and maintenance of new synapses, thus acting as local “tags” for protein synthesis-dependent synaptic growth during late-phase plasticity.
Highlights
Various forms of synaptic plasticity including long-term potentiation (LTP) in the hippocampus have stages that correspond to the stages of learning and memory
To investigate the possible contribution of these events to late-phase potentiation, we have addressed three questions: Do these early changes persist and become protein synthesis dependent? What is the nature of the changes? How might they contribute to the late phase? Our results suggest that the onset of potentiation is accompanied by rapid and long-lasting increases in the number of sites where synaptic puncta and structures are assembled
Late-Phase Potentiation Is Accompanied by Long-Lasting Increases in Puncta of Presynaptic and Postsynaptic Proteins, Which Depend on Protein Synthesis
Summary
Various forms of synaptic plasticity including long-term potentiation (LTP) in the hippocampus have stages that correspond to the stages of learning and memory. Early-phase (,1 hr) synaptic plasticity is thought to involve the covalent modification of proteins in existing pre- or postsynaptic structures [1,2]. A number of studies have found that synaptic components undergo continual assembly and disassembly, and late-phase plasticity somehow alters that balance [7,8,9,10,11,12]. It is not known whether the assembly and disassembly occur at random or fixed sites, and whether plasticity alters the number or dynamics of those sites
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