Review

Errant gardeners: glial-cell-dependent synaptic pruning and neurodevelopmental disorders

  • Nature Reviews Neuroscience volume 18, pages 658670 (2017)
  • doi:10.1038/nrn.2017.110
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Abstract

The final stage of brain development is associated with the generation and maturation of neuronal synapses. However, the same period is also associated with a peak in synapse elimination — a process known as synaptic pruning — that has been proposed to be crucial for the maturation of remaining synaptic connections. Recent studies have pointed to a key role for glial cells in synaptic pruning in various parts of the nervous system and have identified a set of critical signalling pathways between glia and neurons. At the same time, brain imaging and post-mortem anatomical studies suggest that insufficient or excessive synaptic pruning may underlie several neurodevelopmental disorders, including autism, schizophrenia and epilepsy. Here, we review current data on the cellular, physiological and molecular mechanisms of glial-cell-dependent synaptic pruning and outline their potential contribution to neurodevelopmental disorders.

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Acknowledgements

U.N. has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 705452, International Brain Research Organization Return Home Fellowship, and L'ORÉAL Baltic “For Women In Science” fellowship with the support of the Lithuanian National Commission for the United Nations Educational, Scientific and Cultural Organization (UNESCO) and the Lithuanian Academy of Sciences.

Author information

Affiliations

  1. Department of Neurobiology and Biophysics, Life Science Center, Vilnius University, Sauletekio al. 7, LT-10257 Vilnius, Lithuania.

    • Urte Neniskyte
  2. Epigenetics and Neurobiology Unit, European Molecular Biology Laboratory (EMBL), Via Ramarini 32, 00015 Monterotondo, Italy.

    • Cornelius T. Gross

Authors

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Contributions

U.N. and C.T.G. researched data for the article, made substantial contributions to discussions of the content, wrote the article and reviewed and/or edited the manuscript before submission.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Cornelius T. Gross.

Glossary

Neuromuscular junction

(NMJ). A peripheral synapse between one or more motor neurons and the motor endplate on a skeletal muscle fibre.

Receptive fields

Particular regions of a sensory space, such as the visual field, in which a stimulus will modify the firing of an individual sensory neuron.

Topographic mappings

Ordered projections of a sensory surface, such as the retina, to one or more structures of the central nervous system (such as the lateral geniculate nucleus and the visual cortex).

Climbing fibres

Axons of inferior olivary neurons that form excitatory synapses with Purkinje cells in the cerebellum.

Bergmann glia

Radial astrocytes in the cerebellar cortex that are involved in early cerebellar development, glutamate diffusion control, synaptogenesis and synaptic pruning.

Minocycline

A tetracycline antibiotic that has been shown to inhibit inflammatory activation of microglia by blocking the nuclear translocation of the pro-inflammatory transcription factor nuclear factor-κB.

Retinal waves

Spontaneous bursts of action potentials that propagate in a wave-like fashion across the developing retina.

Apolipoprotein E

(APOE). A major cholesterol carrier that is also hypothesized to serve as an opsonin. The APOE*4 allele is a major genetic risk factor for Alzheimer disease.

Opsonin

A protein, such as an antibody or complement protein, that binds to a phagocytic target (such as a pathogen), thus rendering it more susceptible to phagocytosis, in a process known as opsonization.

Archicortex

A phylogenetically old part of the cerebral cortex that constitutes the hippocampal formation.

Synaptic multiplicity

A feature of mature circuits in which afferent inputs make more than one synapse onto a single target neuron.

Window-on-the-brain technology

A technique in which the skull is thinned or opened and capped with a transparent implant to allow two-photon or near-infrared in vivo imaging of cortical function.

Autism spectrum disorder

(ASD). A group of neurodevelopmental conditions characterized by social deficits, impaired language development, intellectual disability, increased repetitive or restrictive behaviours and motor abnormalities.

Peripheral benzodiazepine receptor

Translocator protein (TSPO) of the outer mitochondrial membrane that modulates bursts of reactive oxygen species in macrophages, including microglia, and is therefore used as a marker of inflammation.

Penetrant

Of a mutation, producing expression of associated phenotypic traits in a large proportion of individuals carrying the mutation.

Autophagy

An intracellular self-degradative process for orderly degradation and recycling of cellular components and balancing sources of energy at critical periods.

Microgliosis

An intense inflammatory activation of microglia in response to insults to the CNS (such as infection, trauma or neuronal damage).

Ocular dominance index

The difference between contralateral response and ipsilateral response divided by the sum of contralateral and ipsilateral responses.