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  • Review Article
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Activity-dependent regulation of dendritic growth and patterning

Key Points

  • Dendritic morphology is tightly regulated during development and in the adult brain, reflecting its relevance to neuronal function. Both activity-dependent and activity-independent mechanisms participate in the growth and branching of dendrites.

  • In many parts of the nervous system, dendritic arborizations are oriented in specific ways to receive their synaptic inputs. The fact that neurons of the same type bear striking similarities in their morphology, and that this is repeated from animal to animal, indicates that there is a genetic component to the regulation of dendritic morphology.

  • The growth and patterning of dendrites can also be influenced by environmental signals, such as retrograde feedback from their targets and interactions with neighbouring cells of the same kind. Several molecules that mediate these effects have been identified. They include semaphorin 3A, Slit1, Notch and brain-derived neurotrophic factor.

  • In many different species and brain structures, there is a close correlation between the arrival of afferents and dendritic maturation. This effect of afferent fibres occurs at two levels — they influence dendritic growth and regulate dendritic patterning. Similarly, the effects of afferent fibres depend on two factors — the arrival of the afferent axon and its synaptic output. Most studies have focused on the role of synaptic activity on dendritic development.

  • The signalling pathways that are activated in response to synaptic activity to affect dendritic development are not fully understood, but calcium seems to be a crucial messenger. The effects of calcium can be global (for example, stimulating transcription through the activation of calcium/calmodulin-dependent protein kinase IV and cAMP-response-element-binding protein) or local (for example, acting on the cytoskeleton to stabilize growing dendrites). However, our understanding of the role of calcium on dendritic development remains rudimentary, and the signalling pathways that are involved in its effects remain to be precisely identified.

Abstract

One of the most remarkable features of the developing brain is its ability to undergo structural change in response to experience. Among the cellular elements that show this kind of plasticity are dendrites, which are the components that receive and process synaptic information. Recent observations indicate that calcium signalling in neurons can regulate dendritic growth and remodelling by several mechanisms, and these mechanisms are likely to be key mediators of structural plasticity in the developing brain.

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Figure 1: Dendritic arborizations of mature central neurons have distinct morphologies.
Figure 2: Two examples of central neurons that undergo dendritic remodelling to refine their connectivity.
Figure 3: Schematic of mechanisms that might mediate calcium-dependent dendritic growth.
Figure 4: Local elevations in intracellular calcium might contribute to dendritic remodelling in vivo.
Figure 5: Representation of how calcium signals might regulate dendritic growth and patterning during development.

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Acknowledgements

This work is supported by grants from the National Institute of Neurological Disorders and Stroke and the March of Dimes Birth Defects Foundation (A.G.), and from the National Institutes of Health and the National Science Foundation (R.O.L.W.).

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Correspondence to Anirvan Ghosh.

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DATABASES

LocusLink

AMPA receptors

BDNF

CaMKII

CaMKIV

CREB

gelsolin

MAPK

nAChRs

NMDA receptors

Notch

Rac

RhoA

Sema3A

Slit1

VGCCs

FURTHER INFORMATION

Encyclopedia of Life Sciences

dendrites

dendritic spines

neural activity and the development of brain circuits

synapses

Glossary

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 so-called en passant synapses with this cell type.

BARREL

A cylindrical column of neurons that is found in the rodent neocortex. Each barrel receives sensory input from a single whisker follicle, and the topographical organization of the barrels corresponds precisely to the arrangement of whisker follicles on the face.

GLOMERULUS

Axon terminals end in a variety of configurations within the neuropil. The most common is en passant or de passage, in which axons make simple synapses as they pass dendrites or cell bodies. By contrast, some axons end in — or produce strings of — enlargements that are often packed with synaptic vesicles. These glomerular-type endings synapse with large numbers of dendrites and other axons clustered around the glomerular ending.

INNER PLEXIFORM LAYER

The retinal layer that is formed by synaptic contacts between the bipolar, the amacrine and the ganglion cells.

WEAVER

This mouse strain is characterized by cerebellar abnormalities and ataxia, which are associated with a mutation in an inwardly rectifying potassium channel.

REELER

A mutant mouse that is characterized by tremors, dystonia and ataxia. These phenotypes are associated with mutations in a protein known as reelin.

DARK REARING

An experimental condition in which an animal is reared in total darkness so that only endogenous activity is present in the developing visual system.

CLIMBING FIBRES

Cerebellar afferents that arise from the inferior olivary nucleus, each of which forms multiple synapses with a single Purkinje cell.

OCULAR DOMINANCE COLUMNS

In the mature primary visual cortex of mammals, most neurons respond predominantly to visual inputs from one eye or the other. Cells that respond to a given eye are arranged in stripes — the ocular dominance columns — that alternate with stripes of neurons that respond to the other eye.

DOMINANT NEGATIVE

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

BALLISTIC METHOD

A transfection method in which the gene of interest is used to coat gold particles, which are then 'fired' into the biological sample using an air gun.

CAGED CALCIUM

In general terms, a caged molecule is a labile derivative of a biologically active molecule that will break down after appropriate (commonly luminous) stimulation to yield the bioactive compound.

RHO GTPASES

A family of proteins that are related to the product of the Ras oncogene and are involved in controlling the polymerization of 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.

FILOPODIA

Long, thin protrusions that are present at the periphery of migrating cells and growth cones. They are largely composed of F-actin bundles.

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Wong, R., Ghosh, A. Activity-dependent regulation of dendritic growth and patterning. Nat Rev Neurosci 3, 803–812 (2002). https://doi.org/10.1038/nrn941

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