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  • Review Article
  • Published:

Actin in action: the interplay between the actin cytoskeleton and synaptic efficacy

Nature Reviews Neuroscience volume 9, pages 344–356 (2008)Cite this article

A Corrigendum to this article was published on 01 June 2008

Key Points

  • Actin filaments are the major cytoskeletal elements of pre- and postsynaptic terminals.

  • Actin exists in two states in the cell: as monomeric G-actin and as a two-stranded polar helical filament (F-actin) composed of G-actin. F-actin preferentially polymerizes at the barbed end of the filament and depolymerizes at the opposite, pointed end. A variety of actin-binding proteins influence the structure and organization of the actin cytoskeleton.

  • By engaging actin regulatory proteins, synaptic activity can remodel both the pre- and the postsynaptic actin cytoskeleton.

  • In the presynaptic terminal, actin is involved in maintaining and regulating synaptic vesicle pools, probably by serving as a scaffold to restrict vesicle mobility and by providing tracks to direct the transfer of vesicles between pools. At the active zone, actin can regulate vesicle docking and priming. Actin also facilitates the endocytic retrieval of synaptic vesicles.

  • Recent findings show that actin dynamics are required for the sharing of synaptic vesicles between boutons along the axon, and that promoting actin polymerization is sufficient to unsilence presynaptic boutons in young neurons.

  • At postsynaptic terminals, different pools of actin are specialized for the synaptic anchoring and exo–endocytic trafficking of neurotransmitter receptors.

  • Most excitatory synapses are made onto dendritic spines that are enriched for F-actin. The size of dendritic spines positively correlates with the number of glutamate receptors at the postsynaptic density.

  • Induction of synaptic plasticity changes the size and shape of spines, at least in part by reorganizing the underlying actin cytoskeleton. With LTP, spines become larger and increase their relative content of F-actin; with LTD, spines shrink and depolymerize their F-actin.

  • The signalling pathways responsible for structural and functional synaptic plasticity diverge considerably, and conditions can be found for uncoupling the two processes. Under normal conditions, however, structural and functional modifications are interdependent and coordinated.

  • Dysfunctions in synaptic actin dynamics have significant consequences for cognition and are closely associated with neurological disorders and dementia.

Abstract

Synapse regulation exploits the capacity of actin to function as a stable structural component or as a dynamic filament. Beyond its well-appreciated role in eliciting visible morphological changes at the synapse, the emerging picture points to an active contribution of actin to the modulation of the efficacy of pre- and postsynaptic terminals. Moreover, by engaging distinct pools of actin and divergent signalling pathways, actin-dependent morphological plasticity could be uncoupled from modulation of synaptic strength. The aim of this Review is to highlight some of the recent progress in elucidating the role of the actin cytoskeleton in synaptic function.

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Figure 1: Overview of actin at the excitatory synapse.
Figure 2: Actin and the synaptic vesicle cycle.
Figure 3: A model for structural and functional spine plasticity.

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Acknowledgements

Research in the authors' laboratory is supported by the Medical Research Council and the European Commission Framework VI (EU Synapse project, LSHM-CT-2005-019055).

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Authors and Affiliations

  1. MRC Laboratory for Molecular Cell Biology and MRC Cell Biology Unit, University College London, Gower Street, London, WC1E 6BT, UK

    Lorenzo A. Cingolani & Yukiko Goda

  2. Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK

    Yukiko Goda

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Glossary

Long-term potentiation

(LTP). Long-lasting (hours to days) enhancement of synaptic communication between two neurons as a consequence of their simultaneous activity. It is one of the most highly studied cellular models for learning and memory.

Vesicle docking

The attachment of synaptic vesicles to the active zone of the presynaptic terminal.

Vesicle priming

ATP-dependent pre-fusion reactions that prepare docked synaptic vesicles for Ca2+-dependent exocytosis.

Active zone

The portion of the presynaptic membrane where synaptic vesicle exocytosis occurs.

Readily releasable pool

The pool of synaptic vesicles that are immediately available for exocytosis. These vesicles are thought to be the docked and primed vesicles at the active zone and constitute ∼1–2% of all vesicles.

Recycling pool

The pool of synaptic vesicles that engage in and support neurotransmitter release at moderate stimulation intensities. They represent ∼5–50% of all synaptic vesicles.

Reserve pool

The pool of synaptic vesicles that can engage in neurotransmitter release during intense stimulation. They constitute the majority of synaptic vesicles (∼50–90%). At some synapses, not all reserve-pool vesicles are used for neurotransmitter release, and the function of these vesicles remains to be established.

Bouton

The button-like swelling or small protuberance on an axon that harbours the presynaptic assembly for neurotransmitter release (that is, the presynaptic terminal).

Fluorescence recovery after photobleaching

(FRAP). A technique that provides measurements of the lateral mobility and dynamics of fluorescently labelled molecules in living cells.

Neuromuscular junction

(NMJ). A synapse between a motor neuron axon and the muscle that it innervates.

SNARE complex

(Soluble NSF attachment protein (SNAP)-receptor complex). A trimeric complex formed between synaptobrevin on synaptic vesicles and syntaxin and SNAP-25 on the plasma membrane that is essential for membrane fusion.

Postsynaptic density

(PSD). The electron-dense region of the postsynaptic membrane that is directly apposed to the active zone. It contains neurotransmitter receptors, scaffold proteins, cell-adhesion molecules and signalling proteins.

Fluorescence resonance energy transfer

(FRET). A spectroscopic technique that uses the direct transfer of energy from one fluorophore to another to measure the distance between the fluorophores.

Long-term depression

(LTD). Long-lasting (hours to days) weakening of synaptic communication between two neurons, generally as a consequence of persistent weak neuronal activity. Along with LTP, LTD is intensively studied as a cellular model for learning and memory.

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Cingolani, L., Goda, Y. Actin in action: the interplay between the actin cytoskeleton and synaptic efficacy. Nat Rev Neurosci 9, 344–356 (2008). https://doi.org/10.1038/nrn2373

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