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Experience-dependent structural synaptic plasticity in the mammalian brain

An Erratum to this article was published on 21 August 2009

Key Points

  • Long-term, high-resolution imaging studies of neuronal structure in vivo have revealed that structural plasticity is an ongoing process in the adult brain of mammals, even under baseline conditions.

  • The large-scale structure of cortical neurons, which consists of axonal and dendritic branches, is relatively stable under most conditions. By contrast, small synaptic structures, such as dendritic spines and axonal boutons are highly dynamic, displaying size changes and changes in cytoskeletal dynamics.

  • Although most dendritic spines and axonal boutons are maintained over a large fraction of the animal's life, a subpopulation appears and disappears. For both spines and boutons the turnover is balanced, leaving the total density unchanged under baseline conditions.

  • The sizes of spines and synapses are maintained and regulated through dynamic interactions between their molecular constituents, which are dymaically re-allocated among synapses.

  • New spines are mostly transient. They rarely turn into persistent spines. Persistent spines always bear synapses.

  • Changes in sensory experience and learning cause the stabilization of new spines in cortical areas that display functional changes, indicating that synapse formation and elimination probably contribute to experience-dependent rewiring of cortical circuits.

  • Structural plasticity might have a role in functional network alterations in neurodegenerative and memory disorders, and may also underlie spontaneous recovery of function after local brain injury and peripheral nerve lesions.

Abstract

Synaptic plasticity in adult neural circuits may involve the strengthening or weakening of existing synapses as well as structural plasticity, including synapse formation and elimination. Indeed, long-term in vivo imaging studies are beginning to reveal the structural dynamics of neocortical neurons in the normal and injured adult brain. Although the overall cell-specific morphology of axons and dendrites, as well as of a subpopulation of small synaptic structures, are remarkably stable, there is increasing evidence that experience-dependent plasticity of specific circuits in the somatosensory and visual cortex involves cell type-specific structural plasticity: some boutons and dendritic spines appear and disappear, accompanied by synapse formation and elimination, respectively. This Review focuses on recent evidence for such structural forms of synaptic plasticity in the mammalian cortex and outlines open questions.

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Figure 1: In vivo time-lapse imaging of axonal boutons and dendritic spines.
Figure 2: Retrospective electron microscopy analysis of previously imaged neurons in vivo.
Figure 3: Two modes of synapse formation by spine growth.
Figure 4: Experience-dependent spine plasticity in the adult neocortex.
Figure 5: A model for the relationship between transient spines, persistent spines and circuit plasticity.

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Acknowledgements

We thank V. De Paola, S. Kuhlman, R. Weimer for sharing unpublished figures and V. De Paola, K. Fox, M. Hübener, T. Keck, G. Knott, S. Kuhlman, C. Portera-Cailliau and K. Zito for their input and comments on the manuscript.

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Supplementary information

Supplementary information S1 (table)

In vivo imaging of structural plasticity. (PDF 257 kb)

Supplementary information S2 (Box)

Methods for gene transfer to label sparse subsets of neurons with fluorescent proteins (PDF 361 kb)

Supplementary information S3 (Box)

Surgical preparations for long-term imaging in vivo (PDF 609 kb)

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Glossary

Golgi method

A method that is used to label a sparse subset of neurons in fixed tissue using potassium dichromate and silver nitrate; neurons are stained by microcrystallization of silver chromate. The labelling seems stochastic, but the mechanisms underlying sparse labelling remain unknown.

Critical period

The developmental age when an animal displays a heightened sensitivity to certain environmental stimuli, such as sensory experiences, which impact (often irreversibly) the development of neural circuits.

Optical point spread function

The point spread function (PSF) describes the response of an imaging system to a point object. In microscopy the PSF is a measure of the resolution.

Optophysiological recording

Optical microscopy-based imaging of cellular function, such as calcium imaging.

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Holtmaat, A., Svoboda, K. Experience-dependent structural synaptic plasticity in the mammalian brain. Nat Rev Neurosci 10, 647–658 (2009). https://doi.org/10.1038/nrn2699

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