Synaptic plasticity underlies higher brain function such as learning and memory, and the actin cytoskeleton in dendritic spines composing excitatory postsynaptic sites plays a pivotal role in synaptic plasticity. In this chapter, we review the role of drebrin in the regulation of the actin cytoskeleton during synaptic plasticity, under long-term potentiation (LTP) and long-term depression (LTD). Dendritic spines have two F-actin pools, drebrin-decorated stable F-actin (DF-actin) and drebrin-free dynamic F-actin (FF-actin). Resting dendritic spines change their shape, but are fairly constant over time at steady state because of the presence of DF-actin. Accumulation of DF-actin is inversely regulated by the intracellular Ca2+ concentration. However, LTP and LTD stimulation induce Ca2+ influx through N-methyl-D-aspartate (NMDA) receptors into the potentiated spines, resulting in drebrin exodus via myosin II ATPase activation. The potentiated spines change to excited state because of the decrease in DF-actin and thus change their shape robustly. In LTP, the Ca2+ increase via NMDA receptors soon returns to the basal level, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) expression at the postsynaptic membrane is increased. The Ca2+ recovery and AMPAR increase coordinately induce the re-accumulation of DF-actin and change the dendritic spines from the excited state to steady state during LTP maintenance. During LTD, the prolonged intracellular Ca2+ increase inhibits the re-accumulation of DF-actin, resulting in facilitation of AMPAR endocytosis. Because of the positive feedback loop of the AMPAR decrease and drebrin re-accumulation inhibition, the dendritic spines are instable during LTD maintenance. Taken together, we propose the presence of resilient spines at steady state and plastic spines at excited state and discuss the physiological and pathological relevance of the two-state model to synaptic plasticity.
Keywords: Actin; Ca2+; Dendritic spine; Drebrin exodus; Long-term depression; Long-term potentiation; Myosin.