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  • Review Article
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Dentritic spines : structure, dynamics and regulation

Key Points

  • Dendritic spines are morphological specializations that protrude from the main shaft of dendrites. Most excitatory synapses in the mature mammalian brain occur on spines. So, spines represent the main unitary postsynaptic compartment for excitatory input.

  • Spines have been classified by shape as thin, stubby, mushroom- and cup-shaped. However, spine morphology is not static; spines change size and shape over variable timescales. In addition, most spines exhibit a single, continuous postsynaptic density (PSD), but some PSDs are discontinuous or perforated.

  • What is the significance of dendritic spines? There is no definitive answer to this question, but the prevailing view is that their primary function is to provide a microcompartment for segregating postsynaptic chemical responses, such as elevated calcium.

  • Dendritic filopodia are widely believed to be the precursors of dendritic spines. However, a simple developmental relationship between filopodia and spines does not seem to exist. So, the filopodium–spine transition is unlikely to be a predestined process, but instead one that is reversible and regulated by factors such as synaptic activity.

  • Regulated changes in spine number might reflect mechanisms for converting transient changes in synaptic activity into long-lasting alterations. Indeed, changes in spine density have been observed in response to changes in the efficacy of neurotransmission. In general terms, spines seem to be maintained by an 'optimal' level of synaptic activity: spine density increases when there is insufficient activity, and decreases when stimulation is excessive. Moreover, spine morphology is markedly influenced by the activity of glutamate receptors.

  • Dendritic spines exhibit rapid motility. Most spines can change shape in seconds. The shape change involves a remodelling of the cytoskeleton in the spine, and actin-based protrusive activity from the spine head. The underlying molecular mechanisms of this motile behaviour, and its functional significance, are unknown.

  • Considerable progress has been made in identifying the molecules that control spine growth and maturation. The cytoskeleton is crucial for their development and stability, and an expanding set of actin-binding and actin-regulatory molecules has also been implicated in these processes. They include GTPases of the Rho/Rac/Cdc42 family, the small GTPase Ras, and a series of receptors and scaffold proteins.

  • Several questions remain to be answered in this nascent field. For example, what is the actual function of spines in brain plasticity and behaviour? What are the intrinsic and extrinsic factors that determine the formation of spines? What is the relationship between the structural plasticity of spines, and the movements of molecules and membranes into and out of this postsynaptic compartment?

Abstract

Dendritic spines are tiny protrusions that receive excitatory synaptic input and compartmentalize postsynaptic responses. Heterogeneous in size and shape, and modifiable by activity and experience, dendritic spines have long been thought to provide a morphological basis for synaptic plasticity. Although advanced imaging techniques have highlighted the rapid and regulated motility of spines in living neurons, the functional significance of spine plasticity remains elusive. Recent insights into the molecular mechanisms that regulate spine morphogenesis offer potential ways to manipulate dendritic spines in vivo and to explore their physiological roles in the brain.

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Figure 1
Figure 2: Structure of the dendritic spine.
Figure 3: A model of changes in spine and PSD morphology after LTP.
Figure 4: Shank and Homer are targeted to spines and cause dendritic spine enlargement.

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Correspondence to Morgan Sheng.

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DATABASES

The following terms in this article are linked online to: LocusLink

α-actinin

adducin

cortactin

drebrin

Homer

Kalirin-7

PSD95

Rac1

Rap

Ras

RhoA

Shank

spinophilin

syndecan 2

OMIM

Down's syndrome

epilepsy

fragile-X syndrome

FURTHER INFORMATION

Encyclopedia of Life Sciences

AMPA receptors

dendritic spines

glutamatergic synapses: molecular organization

NMDA receptors

Glossary

LONG-TERM POTENTIATION

A long-lasting increase in the efficacy of neurotransmission, which can be elicited by diverse patterns of synaptic activation.

FILOPODIA

Long, thin protrusions at the periphery of migrating cells and growth cones. They are rich in bundles of F-actin.

TWO-PHOTON 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 approximately as the square 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.

FRAGILE-X SYNDROME

A genetic condition commonly transmitted from mother to son, which is associated with mental retardation, abnormal facial features and enlarged testicles.

TETRODOTOXIN

A potent marine neurotoxin that blocks voltage-gated sodium channels. Tetrodotoxin was originally isolated from the tetraodon pufferfish, and contains a positively charged guanidinium group and a pyrimidine ring.

RHO/RAC/CDC42 GTPASES

Molecules related to the product of the oncogene Ras, which are involved in controlling the polymerization and subsequent organization of actin.

LAMELLIPODIA

Flattened, sheet-like projections from the surface of a cell, which are often associated with cell migration.

DOMINANT NEGATIVE

Describes a mutant molecule that can form a heteromeric complex with the normal molecule, knocking out the activity of the entire complex.

PDZ DOMAIN

A peptide-binding domain that is important for the organization of membrane proteins, particularly at cell–cell junctions, including synapses. They can bind to the carboxyl termini of proteins, or can form dimers with other PDZ domains. PDZ domains are named after the proteins in which these sequence motifs were originally identified (PSD95, Discs-large, zona occludens 1).

RAS PROTEINS

A group of small GTPases involved in growth, differentiation and cellular signalling that require the binding of GTP to enter into their active state.

HEPARAN SULPHATE

A glycosaminoglycan that consists of repeated units of hexuronic acid and glucosamine residues. It usually attaches to proteins through a xylose residue to form proteoglycans.

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Hering, H., Sheng, M. Dentritic spines : structure, dynamics and regulation. Nat Rev Neurosci 2, 880–888 (2001). https://doi.org/10.1038/35104061

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