Role of Drebrin in Synaptic Plasticity

Abstract

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 Ca concentration. However, LTP and LTD stimulation induce Ca 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 Ca 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 Ca 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 Ca 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.

Much More Than a Scaffold: Cytoskeletal Proteins in Neurological Disorders

“…These three elements (neurofilaments, microfilaments, and microtubules) work together to guarantee a proper formation of the nervous system during the embryonic development and to assure its function in adulthood. There are three particular events where the function of cytoskeletal proteins is required: first, during embryonic development, where the cytoskeleton participates in the growth and guidance of axons (for a review see, [13,14]); second, during adult life, where neurons depend on the cytoskeleton for maintaining neuronal homeostasis and neuronal plasticity [15][16][17][18]; and third, when the peripheral axon needs to regenerate after being injured. In this last event, peripheral neurons (for a review, see [19]) require a specific set of cytoskeletal proteins to ensure nerve regeneration upon damage [20,21].…”

NMDA receptor‐dependent and ‐independent effects of natural compounds and crude drugs on synaptic states as revealed by drebrin imaging analysis

“…As previously mentioned, drebrin exodus occurs during the initial stage of synaptic plasticity, such as LTP and LTD. However, during LTP stimulation, the drebrin exodus is transient (Sekino et al., 2017). Whether these drugs induce LTP or LTD should be investigated by determining whether the drebrin exodus is transient following drug treatment, using the live‐cell imaging of GFP‐drebrin‐transfected neurons (Mizui et al., 2014).…”

Mysterious Mechanisms of Memory Formation: Are the Answers Hidden in Synapses?

“…The Ca2+ recovery and AMPAR increase are harmonized and induce the re-accumulation of DF-actin and change the dendritic spines from the excited state to a steady state during LTP maintenance. AMPAR endocytosis is facilitated due to the inhibition of re-accumulation of DF-actin caused by a prolonged increase in intracellular Ca2+ during LTD. Because of the positive feedback loop during AMPAR decrease and drebrin re-accumulation inhibition, the dendritic spines are found to be unstable during LTD maintenance [22]. The research on the effect of sirtuin 2 (SIRT2) on synaptic plasticity and cognitive function has demonstrated that SIRT2 acts as an AMPAR deacetylation and causes protein accumulation.…”