Research ReportActin dynamics and the evolution of the memory trace

- The synaptic basis of LTP and memory evolves in stages, generation, stabilization and consolidation.
- Actin regulation is critical to each stage.
- Generation requires processes that degrade the actin cytoskeleton in dendritic spines.
- Stabilization requires calcium depended GTPases and integrins to expand and reorganize the actin cytoskeleton in spines.
- Consolidation of the actin cytoskeleton may depend on BDNF and Arc; its properties enable dendritic spines to self sustain.

The goal of this essay is to link the regulation of actin dynamics to the idea that the synaptic changes that support long-term potentiation and memory evolve in temporally overlapping stages-generation, stabilization, and consolidation. Different cellular/molecular processes operate at each stage to change the spine cytoarchitecture and, in doing so, alter its function. Calcium-dependent processes that degrade the actin cytoskeleton network promote a rapid insertion of AMPA receptors into the post synaptic density, which increases a spine׳s capacity to express a potentiated response to glutamate. Other post-translation events then begin to stabilize and expand the actin cytoskeleton by increasing the filament actin content of the spine and reorganizing it to be resistant to depolymerizing events. Disrupting actin polymerization during this stabilization period is a terminal event-the actin cytoskeleton shrinks and potentiated synapses de-potentiate and memories are lost. Late-arriving, new proteins may consolidate changes in the actin cytoskeleton. However, to do so requires a stabilized actin cytoskeleton. The now enlarged spine has properties that enable it to capture other newly transcribed mRNAs or their protein products and thus enable the synaptic changes that support LTP and memory to be consolidated and maintained.This article is part of a Special Issue entitled SI: Brain and Memory.