Key Points
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Dendritic spines were first described more than a hundred years ago, yet their function is still unclear. Insights into the roles of spines in the adult nervous system could be gained by understanding how they originate during development.
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Evidence from the Purkinje cell dendritic tree indicates that spine development has two phases: an initial period of spine proliferation, which is probably intrinsic to the neuron, followed by a decline, which depends on the activity of the synapse and the neuron.
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Spine formation in pyramidal neurons of the neocortex and hippocampus occurs after birth in many species. In the rat neocortex, spine density increases during the first few weeks after birth, then declines with age. The spines also undergo profound morphological rearrangements. These events seem to be influenced by the presynaptic terminal, although the extent to which they depend on neuronal activity is still unclear.
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Two recent studies using in vivo two-photon microscopy investigated the generation and disappearance of spines in the adult cerebral cortex. One study concluded that spines are very stable in the adult brain, whereas the other concluded that there is a high rate of turnover. However, there were inconsistencies between the two studies that might explain this discrepancy.
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Dendritic filopodia are long, thin structures that are present in developing dendrites, and it has been suggested that they serve as spine precursors. Live imaging of intact tissue will be required to test the validity of the filopodial model of spine formation.
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Conflicting data on spinogenesis have emerged from the study of various cell types. The simplest explanation for these controversies is that different populations of spines behave differently. Live imaging studies will enable us to understand the biological diversity of dendritic spines, and to resolve the function of these fascinating yet mysterious organelles.
Abstract
Dendritic spines are small protrusions from many types of neuron, which receive most of the excitatory inputs to the cell. Spines are thought to have important roles in neural information processing and plasticity, yet we still have a poor understanding of how they emerge during development. Here, we review the developmental generation of dendritic spines, covering recent live imaging experiments and older ultrastructural data. We address the potential role of dendritic filopodia in spine development and recent findings of spinogenesis in adult animals, and conclude by discussing three potential models of spinogenesis.
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Acknowledgements
We thank V. Nägerl for Figure 2, and C. Lohmann, C. Mason, C. Portera-Cailliau and N. Ziv for comments. R.Y. is funded by the National Eye Institute and the John Merck Fund. T.B. is funded by the Max-Planck Gesellschaft.
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FURTHER INFORMATION
Glossary
- PURKINJE CELLS
-
Inhibitory neurons in the cerebellum that use GABA (γ-aminobutyric acid) as their neurotransmitter. Their cell bodies are situated beneath the molecular layer, and their dendrites branch extensively in this layer. Their axons project into the underlying white matter, and they provide the only output from the cerebellar cortex.
- PYRAMIDAL NEURONS
-
A class of neuron in the cerebral cortex with a pyramid-shaped cell body. These neurons send long axons down the spinal cord and form dendrites that extend laterally through the cortical layer that contains the cell body.
- FILOPODIA
-
Long, thin protrusions that are present at the periphery of migrating cells and growth cones. They are composed largely of F-actin bundles.
- WEAVER MUTANT MICE
-
This mouse strain is characterized by cerebellar abnormalities and ataxia, which are associated with a mutation in an inwardly rectifying potassium channel.
- REELER MUTANT MICE
-
A mouse strain that is characterized by tremors, dystonia and ataxia. These phenotypes are associated with a deficiency in the production of the reelin protein.
- PARALLEL FIBRES
-
The axons of cerebellar granule cells. Parallel fibres emerge from the molecular layer of the cerebellar cortex towards the periphery, where they extend branches perpendicular to the main axis of Purkinje neurons and form 'en passant' synapses with this cell type.
- CLIMBING FIBRES
-
Cerebellar afferents that arise from the inferior olivary nucleus, each of which forms multiple synapses with a single Purkinje cell.
- TETRODOTOXIN
-
(TTX). A potent marine neurotoxin that blocks voltage-gated sodium channels. TTX was originally isolated from the Tetraodon pufferfish, and contains a positively charged guanidinium group and a pyrimidine ring.
- STAGGERER MOUSE
-
A mouse strain that has a deletion in the gene that codes for the nuclear hormone receptor RORα. The homozygous mutant mouse shows ataxia, which is associated with atrophy of the cerebellum and loss of Purkinje cells. The heterozygous mutant also shows an age-related loss of Purkinje cells, but seems to be phenotypically normal.
- NEUROPIL
-
A felt-like network that is interspersed between the cells of the grey matter in the central nervous system. It consists of neuronal and glial processes and synaptic terminals.
- TWO-PHOTON LASER MICROSCOPY
-
A form of microscopy in which a fluorochrome that would normally be excited by a single photon is stimulated quasi-simultaneously by two photons of lower energy. Under these conditions, fluorescence increases as a function of the square of the light intensity, and decreases as the fourth power of the distance from the focus. Because of this behaviour, only fluorochrome molecules near the plane of focus are excited, greatly reducing light scattering and photodamage of the sample.
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Yuste, R., Bonhoeffer, T. Genesis of dendritic spines: insights from ultrastructural and imaging studies. Nat Rev Neurosci 5, 24–34 (2004). https://doi.org/10.1038/nrn1300
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DOI: https://doi.org/10.1038/nrn1300
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