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.
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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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.
The authors declare no competing financial interests.
In vivo imaging of structural plasticity. (PDF 257 kb)
Methods for gene transfer to label sparse subsets of neurons with fluorescent proteins (PDF 361 kb)
Surgical preparations for long-term imaging in vivo (PDF 609 kb)
- 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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