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Neural development

Less is more: a critical role of synapse pruning in neural circuit wiring

Nature Reviews Neuroscience volume 24, page 61 (2023)Cite this article

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One of the marvels of the brain is its ability to adapt to changes in the environment, especially during early development. This capacity resides largely in synapses, which are the basic building blocks of neural circuits. Rapid synaptogenesis occurs during early postnatal development and is followed by a progressive reduction in synapse number, in a process known as synapse elimination, or pruning, that continues into adolescence and adulthood and is thought to be critical to neural circuit refinement.

Although the concept of synapse pruning is now widely accepted, the idea that the brain would overproduce synapses and then prune some away, rather than getting the numbers right to start with, was quite counterintuitive when it was first proposed. In a seminal paper published in Science in 1986, Rakic et al. provided some of the first convincing evidence of this notion by reporting systematic overproduction of synapses in multiple regions of the primate cerebral cortex. By analysing more than 500,000 synapses captured in 25,000 electron micrographs taken from 5 different cortical regions (collected from Rhesus monkeys at times from 100 to 8,000 days after conception), the authors concluded that overproduction of synapses (compared to the final numbers of synapses in adult animals) occurred concurrently in all cortical layers and regions. By classifying the synapses into asymmetric spine synapses, symmetric shaft synapses and synapses onto somata, they further showed that the subsequent developmental reduction in synapse density mostly involved the removal of spine synapses. Asymmetric spine synapses are mostly glutamatergic, whereas symmetric shaft synapses are mostly GABAergic. The specific change in the ratio of one type of synapse with respect to another suggested that synapse number was actively regulated.

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References

Original article

  • Rakic, P. et al. Concurrent overproduction of synapses in diverse regions of the primate cerebral cortex. Science 232, 232–235 (1986)

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Related article

  • Forrest, M. P. et al. Dendritic structural plasticity and neuropsychiatric disease. Nat. Rev. Neurosci. 19, 215–234 (2018)

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  1. School of Life Sciences, Peking University, Beijing, China

    Xiang Yu

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  1. Xiang Yu
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Correspondence to Xiang Yu.

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Yu, X. Less is more: a critical role of synapse pruning in neural circuit wiring. Nat Rev Neurosci 24, 61 (2023). https://doi.org/10.1038/s41583-022-00665-7

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  • DOI: https://doi.org/10.1038/s41583-022-00665-7

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